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Drug Interactions Between Silimarine and Darunavir/Ritonavir

This study has been completed.
Sponsor:
Collaborators:
IrsiCaixa
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01346982
First received: April 18, 2011
Last updated: September 29, 2011
Last verified: September 2011
History of Changes
  Purpose
This is a clinical trial to characterize drug interactions between silimarine and the protease inhibitor darunavir/ritonavir.

Condition Intervention Phase
HIV
 Drug: Silimarine
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Drug Interactions Between Silimarine And Darunavir/Ritonavir

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Fundacio Lluita Contra la SIDA:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of darunavir [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the plasma concentration-time curve during the dosing interval (AUC0-12) of ritonavir [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]
  • Darunavir and ritonavir clearance (CL/F) [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]
    Change from day 0 in Darunavir and ritonavir clearance at day 14

  • Darunavir and ritonavir volume of distribution (V/F) [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]
  • Darunavir and ritonavir trough concentration in plasma [ Time Frame: DAY 0, day 14 ] [ Designated as safety issue: No ]
  • Adverse events and laboratory abnormalities [ Time Frame: DAY 0, 14, 28 ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events and laboratory abnormalities grade 3 or 4
Estimated Enrollment: 15
Study Start Date: March 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Silimarine
darunavir + ritonavir + silimarine
 Drug: Silimarine
darunavir/ritonavir 600/100 mg + silimarine (150 mg every 8 hours)

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.

  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01346982

Locations
Spain
Lluita contra la Sida Foundation, HIV Unit
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
IrsiCaixa
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  More Information

Responsible Party: Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT01346982     History of Changes
Other Study ID Numbers: SILIDAR  2010-021159-25 
Study First Received: April 18, 2011
Last Updated: September 29, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by Fundacio Lluita Contra la SIDA:
Darunavir
Silimarine
interaction

Additional relevant MeSH terms:
Ritonavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016