Drug Interactions Between Silimarine and Darunavir/Ritonavir

Phase 4

Completed

• Conditions: HIV
• Interventions: Drug: Silimarine

• Registration Number: NCT01346982
• Lead Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Brief Summary

This is a clinical trial to characterize drug interactions between silimarine and the protease inhibitor darunavir/ritonavir.

Detailed Description

The silimarine is the main component of milk thistle (Sylibum marianum), a medicinal herb which, due to its attributed hepatoprotective properties, is widely used by HIV infected patients

15 patients on stable antiretroviral therapy including darunavir/ritonavir 600/100 mg twice a day during four weeks will be enrolled. After their inclusion in the study, patients will receive treatment with silimarine (150 mg every 8 hours) 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 darunavir/ritonavir, and darunavir and ritonavir concentrations in plasma will be determined by high performance liquid chromatography using a validated method.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-04-18
• Study First Submitted QC: 2011-05-03
• Study First Posted: 2011-05-04
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Status Verified: 2011-09
• Last Update Submitted: 2019-11-11
• Last Update Posted: 2019-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Patients receiving antiretroviral therapy containing darunavir / ritonavir at the approved dose of 600/100 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.

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.
• Active alcohol consumption (> 50 g / day) or illicit drugs (except cannabis).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Silimarine	Silimarine	darunavir + ritonavir + silimarine

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of darunavir	DAY 0, day 14

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of ritonavir	DAY 0, day 14
Darunavir and ritonavir clearance (CL/F)	DAY 0, day 14	Change from day 0 in Darunavir and ritonavir clearance at day 14
Darunavir and ritonavir volume of distribution (V/F)	DAY 0, day 14	Change from day 0 in Darunavir and ritonavir volume of distribution at day 14
Darunavir and ritonavir elimination half-life (t1/2) of darunavir and ritonavir	DAY 0, day 14
Darunavir and ritonavir trough concentration in plasma	DAY 0, day 14
Adverse events and laboratory abnormalities	DAY 0, 14, 28	Number of patients with adverse events and laboratory abnormalities grade 3 or 4

Trial Locations

Locations (1)

Lluita contra la Sida Foundation, HIV Unit; 🇪🇸 Badalona, Barcelona, Spain