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

Primary Purpose

HIV Infections, Hyperlipidemia

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Pravastatin
Darunavir
Ritonavir
Pravastatin
Washout
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Pravastatin, Darunavir, Ritonavir, Genetic

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Colorado Denver

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

SLCO1B1 Group 1

SLCO1B1 Group 2

SLCO1B1 Group 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
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)
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
Dosing interval of 24 hours
Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)
Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Dosing interval of 24 hours
Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)

Full Information

First Posted
February 28, 2008
Last Updated
May 20, 2014
Sponsor
University of Colorado, Denver
Collaborators
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
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1. Study Identification

Unique Protocol Identification Number
NCT00630734
Brief Title
Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
Official Title
Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Hyperlipidemia
Keywords
HIV, Pravastatin, Darunavir, Ritonavir, Genetic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SLCO1B1 Group 1
Arm Type
Experimental
Arm Description
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.
Arm Title
SLCO1B1 Group 2
Arm Type
Experimental
Arm Description
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.
Arm Title
SLCO1B1 Group 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pravastatin
Other Intervention Name(s)
Pravachol
Intervention Description
Pravastatin 40 mg by mouth daily on days 1-4
Intervention Type
Drug
Intervention Name(s)
Darunavir
Other Intervention Name(s)
Prezista
Intervention Description
Darunavir 600mg by mouth twice daily on days 12-18
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
Norvir
Intervention Description
Ritonavir 100mg by mouth twice daily on days 12-18
Intervention Type
Drug
Intervention Name(s)
Pravastatin
Other Intervention Name(s)
Pravachol
Intervention Description
Pravastatin 40 mg by mouth daily on days 15-18
Intervention Type
Other
Intervention Name(s)
Washout
Intervention Description
Washout (no medication) on days 5-11.
Primary Outcome Measure Information:
Title
Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Description
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.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Title
Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)
Description
Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Secondary Outcome Measure Information:
Title
Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Description
Dosing interval of 24 hours
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Title
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
Title
Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Description
Dosing interval of 24 hours
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Title
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
Other Pre-specified Outcome Measures:
Title
Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Description
AUC of darunavir over a 12-hour dosing interval.
Time Frame
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Title
Darunavir Maximum Plasma Concentration (Cmax)
Description
Cmax of darunavir over a 12-hour dosing interval
Time Frame
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Title
Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Description
AUC of ritonavir over a 12-hour dosing interval.
Time Frame
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Title
Ritonavir Maximum Plasma Concentration (Cmax)
Description
Cmax of ritonavir over a 12-hour dosing interval
Time Frame
0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina L Aquilante, PharmD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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