Drug Interactions Between Silimarine and Darunavir/Ritonavir

HIV Clinical Trial

Official title:

Drug Interactions Between Silimarine And Darunavir/Ritonavir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01346982
• Other study ID #: SILIDAR
• Secondary ID: 2010-021159-25
• Status: Completed
• Phase: Phase 4
• Start date: March 2011
• Est. completion date: July 2011

Study information

• Verified date: September 2011
• Source: Fundacio Lluita Contra la SIDA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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).

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Silimarine
darunavir/ritonavir 600/100 mg + silimarine (150 mg every 8 hours)

Locations

Country	Name	City	State
Spain	Lluita contra la Sida Foundation, HIV Unit	Badalona	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Fundacio Lluita Contra la SIDA	Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, IrsiCaixa

Country where clinical trial is conducted

Spain, 

Outcome

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