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Trial record 16 of 30 for:    " February 13, 2008":" March 14, 2008"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Hyperlipidemia
Drug: Pravastatin
Drug: Darunavir
Drug: Ritonavir
Other: Washout
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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


Enrollment: 32
Study Start Date: February 2008
Study Completion Date: September 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00630734

Locations
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Principal Investigator: Christina L Aquilante, PharmD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00630734     History of Changes
Other Study ID Numbers: 07-0272, TMC114HIV4003
Study First Received: February 28, 2008
Results First Received: September 12, 2011
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
HIV
Pravastatin
Darunavir
Ritonavir
Genetic

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hyperlipidemias
Dyslipidemias
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Lipid Metabolism Disorders
Metabolic Diseases
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Darunavir
Pravastatin
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Anticholesteremic Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 27, 2014