Drug Interactions Between Echinacea Purpurea and Etravirine

Study Overview
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Brief Summary
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The purpose of this clinical trial is to characterize drug interactions between one medicinal herb: Echinacea purpurea and the protease inhibitor etravirine.

Detailed Description
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Because of its CYP3A4 inducer activity in the liver but its inhibitor effect at the intestinal site, concomitant administration of Equinacea purpurea (a medicinal herb frequently used by HIV-infected patients) and etravirine (an HIV reverse transcriptase inhibitor) might result in clinically relevant pharmacokinetic drug interactions. 15 HIV-infected patients on stable antiretroviral therapy including etravirine at the dosage of 200 mg twice daily during at least 4 weeks will be enrolled. After their inclusion in the study, patients will receive Echinacea purpurea root (500 mg every 8 hours) in addition to their antiretroviral treatment, from day 1 until two weeks later (day 14). On days 0 and 14, blood samples will be drawn immediately before and 1, 2, 4, 6, 8, 10 and 12 hours after the administration of an etravirine dose, and etravirine concentrations in plasma will be determined by high performance liquid chromatography using a validated method.

Official Title
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DRUG INTERACTIONS BETWEEN ECHINACEA PURPUREA AND ETRAVIRINE

Conditions
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HIV

Intervention / Treatment
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* Dietary Supplement: Echinacea purpurea


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients infected with HIV-1 (at least one documented positive Western-Blot). Age 18 years or more. Patients receiving antiretroviral therapy including etravirine at the approved dose of 200 mg twice daily for at least 4 weeks HIV viral load in plasma <50 copies / mL Absence of acute infections and / or tumors in the three months prior to inclusion. Subject able to follow the treatment period, without suspicion of poor adherence in previous antiretroviral treatments. Voluntary written informed consent. Exclusion criteria: Any clinical or historical observation that could interfere with the pharmacokinetics of medications, such as gastrointestinal illness or surgery (except for herniotomy and appendectomy), changes in the composition of plasma proteins, some indication of hepatic or renal dysfunction. Antiretroviral regimen including drugs ritonavir or atazanavir (CYP3A4 inhibitors) Concomitant treatment with drugs inductors of CYP3A4 (rifampicin, fenitoin, carbamazepin, ...) Active alcohol consumption (> 50 g / day) or illicit drugs (except cannabis). Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etravirine + echinacea<br>etravirine + root of Echinacea purpurea | Dietary Supplement: Echinacea purpurea<br>* Patients will take Echinacea purpurea (500 mg every 8 hours) during 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma concentration of etravirine. | plasma concentration of etravirine. | Change from baseline to day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance (CL/F) |  | Change from baseline to day 14 | 
| Volume of distribution (V/F) |  | Change from baseline to day 14 | 
| Elimination half-life (t1/2) |  | Change from baseline to day 14 | 
| Area under the plasma concentration-time curve during the dosing interval (AUC0-24) |  | Change from baseline to day 14 | 
| Number of patients with adverse events |  | From baseline to day 28 | 
| HIV Viral load in plasma |  | Day 14 | 
| Number of patients with laboratory alterations |  | From baseline to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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etravirine, Echinacea purpurea, interaction