Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin

This study has been completed.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00630734
First received: February 28, 2008
Last updated: November 19, 2012
Last verified: November 2012

February 28, 2008
November 19, 2012
February 2008
October 2009   (final data collection date for primary outcome measure)
  • Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
    AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.
  • Relative Change in Pravastatin Maximum Plasma Concentration (Cmax) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
    Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.
Change in pravastatin AUC when pravastatin is administered with and without darunavir/ritonavir. [ Time Frame: multiple dose pravastatin (4 days) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00630734 on ClinicalTrials.gov Archive Site
  • Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
    Dosing interval of 24 hours
  • Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
  • Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
    Dosing interval of 24 hours
  • Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose ] [ Designated as safety issue: No ]
Change in pravastatin Cmax, tmax, t1/2, and oral clearance when pravastatin is administered with and without darunavir/ritonavir. [ Time Frame: multiple dose pravastatin (4 days) ] [ Designated as safety issue: No ]
  • Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    AUC of darunavir over a 12-hour dosing interval.
  • Darunavir Maximum Plasma Concentration (Cmax) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Cmax of darunavir over a 12-hour dosing interval
  • Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    AUC of ritonavir over a 12-hour dosing interval.
  • Ritonavir Maximum Plasma Concentration (Cmax) [ Time Frame: 0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Cmax of ritonavir over a 12-hour dosing interval
Not Provided
 
Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.

Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Hyperlipidemia
  • Drug: Pravastatin
    Pravastatin 40 mg by mouth daily on days 1-4
    Other Name: Pravachol
  • Drug: Darunavir
    Darunavir 600mg by mouth twice daily on days 12-18
    Other Name: Prezista
  • Drug: Ritonavir
    Ritonavir 100mg by mouth twice daily on days 12-18
    Other Name: Norvir
  • Drug: Pravastatin
    Pravastatin 40 mg by mouth daily on days 15-18
    Other Name: Pravachol
  • Other: Washout
    Washout (no medication) on days 5-11.
  • Experimental: SLCO1B1 Group 1
    Participants with the SLCO1B1 *1A/*1A diplotype; Interventions: pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
    Interventions:
    • Drug: Pravastatin
    • Drug: Darunavir
    • Drug: Ritonavir
    • Drug: Pravastatin
    • Other: Washout
  • Experimental: SLCO1B1 Group 2
    Participants with the SLCO1B1 *1A/*1B or *1B/*1B diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
    Interventions:
    • Drug: Pravastatin
    • Drug: Darunavir
    • Drug: Ritonavir
    • Drug: Pravastatin
    • Other: Washout
  • Experimental: SLCO1B1 Group 3
    Participants who carry at least one SLCO1B1 *5, *15, or *17 diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
    Interventions:
    • Drug: Pravastatin
    • Drug: Darunavir
    • Drug: Ritonavir
    • Drug: Pravastatin
    • Other: Washout
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
September 2010
October 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy, HIV-negative volunteers

Exclusion Criteria:

  • Currently active or chronic cardiovascular, hepatic, renal, pancreatic, gastrointestinal, neurologic, hematologic, psychiatric, metabolic, respiratory, inflammatory, or infectious disease
  • Chronic pancreatitis
  • History of rhabdomyolysis
  • History of statin-associated myopathy
  • Active malignancy
  • History of significant skin disease, food allergy, drug allergy, dermatitis, eczema, psoriasis
  • Pregnancy/breastfeeding
  • HIV positive and/or AIDS
  • serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN]);
  • hemoglobin grade 1 or greater (≤ 10.9 g/dL);
  • platelet count grade 1 or greater (≤ 124.999 x 109/L);
  • absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L);
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN);
  • total bilirubin grade 1 or greater (≥ 1.1 x ULN)
  • serum lipase grade 1 or greater (≥ 1.1 x ULN)
  • serum amylase grade 1 or greater (≥ 1.1 x ULN)
  • any other laboratory abnormality of grade 2 or above
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00630734
07-0272, TMC114HIV4003
Yes
University of Colorado, Denver
University of Colorado, Denver
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Principal Investigator: Christina L Aquilante, PharmD University of Colorado, Denver
University of Colorado, Denver
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP