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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 4

Conditions: Hyperlipidemia; HIV Infections

Treatments: Drug: Pravastatin; Drug: Ritonavir; Drug: Darunavir; Other: Washout

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00630734

07-0272

TMC114HIV4003

Details and patient eligibility

About

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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 3 patient groups

SLCO1B1 Group 1

Experimental group

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.

Treatment:

Drug: Darunavir

Drug: Pravastatin

Other: Washout

Drug: Pravastatin

Drug: Ritonavir

SLCO1B1 Group 2

Experimental group

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.

Treatment:

Drug: Darunavir

Drug: Pravastatin

Other: Washout

Drug: Pravastatin

Drug: Ritonavir

SLCO1B1 Group 3

Experimental group

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.

Treatment:

Drug: Darunavir

Drug: Pravastatin

Other: Washout

Drug: Pravastatin

Drug: Ritonavir