Systematic determination of the pharmacokinetic interactions of Echinacea purpurea with prescribed medications in healthy volunteers: A phase-I clinical trial using a cocktail approach

Recruitment & Eligibility

Status: Recruiting withdrawn before recruiting started

Sex: All

Target Recruitment: 49

Inclusion Criteria

1. Subject gives informed consent by means of a personally signed and dated informed consent form (ICF)
2. Age 18-54 years

Exclusion Criteria

1.Smoking
2.Participants who are genetically carriers of CYP2D6*3-6/*3-6, CYP2C9*2/*3 or *3/*3, CYP3A*22, CYP2C19*2/*2 or SLCO1B1*5/*5
3.Subjects currently enrolled in another clinical trial
4.Usage of medicinal products (prescription and OTC) during the study period, excluding non-hormonal contraceptives
5.Consumption of grapefruit and bitter orange during the study period
6.Consumption of alcohol, tea, herbal supplements or caffeine within 24 hours prior to and during each in-patient study day
7.Hypersensitivity, allergy or idiosyncratic reaction to the IMPs
8.Specific contraindication to the IMPs not covered by other exclusion criteria:
8.1.History of apnoea/respiratory insufficiency (midazolam, codeine)
8.2.History of myopathy (pitavastatin, rosuvastatin)
8.3.History of immune disorders/atopy or tuberculosis/sarcoidosis (Echinacea)
8.4.Known CYP2D6-ultra-rapid-phenotype (codeine)
8.5.Known risk factors for bleeding like gastrointestinal lesions, recent neurosurgery or damages to brain/spine, oesophageal varices, arteriovenous malformations (dabigatran)
9.History of coagulation disorders, abnormal clotting lab results or pharmaceutical anti-coagulation
10.Estimated Glomerular Filtration Rate < 80 ml/min
11.Known active hepatitis B or C infection, acute liver malfunction or abnormal liver lab results
12.Elevated creatinine kinase (as judged by the investigator)
13.Persistent diarrhea
14.Pregnancy and breastfeeding
15.Any other disease, condition or safety laboratory result which might compromise significantly the hematopoietic, renal, pulmonary, hepatic, cardiovascular, immunological, central nervous, dermatological, endocrinological or psychiatric or any other body system (as judged by the investigator)
16.Expected or suspected non-compliance, e.g., major cognitive or psychiatric disorders, drug usage
17.Subjects who are scheduled to undergo hospitalization during the study period
18.Legal incapacity
19.Women of child-bearing potential and not on highly-effective (Pearl-Index <1%) non-hormonal contraception
20.Medical students who are before or in a semester with pharmacological courses and examination at Kiel University

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Changes in bioavailability (measured as AUC (parent)) after 20 days of Echinacea ingestion compared to baseline for dabigatran, pitavastatin and rosuvastatin (indicative for the activity of ABCB1, SLCO1B1 and ABCG2, resp.<br><br>Changes in bioavailability (measured as AUC_parent) after 20 days of Echinacea ingestion compared to baseline for 6 drugs caffeine, midazolam, codeine, morphine, losartan, omeprazole (indicative for the activity of various cytochrome p450 enzymes).<br><br>Statistical and clinical relevance is assumed when the 90% confidence interval of AUCinf(parent, baseline) / AUCinf(parent, after 20 days) is not within the no-effect-boundaries 0.8 – 1.25.

Secondary Outcome Measures

Name	Time	Method
- Pinpointing changes of AUC to a specific metabolic pathway by analyzing changes in metabolic ratios (measured as AUC (parent)/AUC (metabolite)) after 20 days of Echinacea ingestion compared to baseline for 6 parent drug:metabolite pairs to estimate which enzyme might be responsible for the increased metabolic rate<br>- Evaluation of limited sampling strategies<br>- Full pharmacokinetic characterization of the probe drug cocktail<br>- Time-course of induction<br>- Echinaea plasma concentration<br>- Safety profile