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

NCT ID: NCT00630734

Last Updated: 2014-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-09-30

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.

Conditions

HIV Infections; Hyperlipidemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 1-4

Darunavir

Intervention Type: DRUG

Darunavir 600mg by mouth twice daily on days 12-18

Ritonavir

Intervention Type: DRUG

Ritonavir 100mg by mouth twice daily on days 12-18

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 15-18

Washout

Intervention Type: OTHER

Washout (no medication) on days 5-11.

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.

Group Type: EXPERIMENTAL

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 1-4

Darunavir

Intervention Type: DRUG

Darunavir 600mg by mouth twice daily on days 12-18

Ritonavir

Intervention Type: DRUG

Ritonavir 100mg by mouth twice daily on days 12-18

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 15-18

Washout

Intervention Type: OTHER

Washout (no medication) on days 5-11.

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.

Group Type: EXPERIMENTAL

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 1-4

Darunavir

Intervention Type: DRUG

Darunavir 600mg by mouth twice daily on days 12-18

Ritonavir

Intervention Type: DRUG

Ritonavir 100mg by mouth twice daily on days 12-18

Pravastatin

Intervention Type: DRUG

Pravastatin 40 mg by mouth daily on days 15-18

Washout

Intervention Type: OTHER

Washout (no medication) on days 5-11.

Interventions

Pravastatin

Pravastatin 40 mg by mouth daily on days 1-4

Intervention Type: DRUG

Darunavir

Darunavir 600mg by mouth twice daily on days 12-18

Intervention Type: DRUG

Ritonavir

Ritonavir 100mg by mouth twice daily on days 12-18

Intervention Type: DRUG

Pravastatin

Pravastatin 40 mg by mouth daily on days 15-18

Intervention Type: DRUG

Washout

Washout (no medication) on days 5-11.

Intervention Type: OTHER

Other Intervention Names

Pravachol; Prezista; Norvir; Pravachol

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christina L Aquilante, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver

Aurora, Colorado, United States

Countries

United States

Other Identifiers

TMC114HIV4003

Identifier Type: -

Identifier Source: secondary_id

07-0272

Identifier Type: -

Identifier Source: org_study_id