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

Condition(s) targeted: HIV Infections; Hyperlipidemia

Intervention: Pravastatin (Drug); Darunavir (Drug); Ritonavir (Drug); Pravastatin (Drug); Washout (Other)

Phase: Phase 4

Status: Completed

Sponsored by: University of Colorado, Denver

Official(s) and/or principal investigator(s):
Christina L Aquilante, PharmD, Principal Investigator, Affiliation: University of Colorado, Denver

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.

Official title: Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval

Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)

Secondary outcome:

Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval

Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)

Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval

Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

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

University of Colorado Denver, Aurora, Colorado 80045, United States

Starting date: February 2008
Last updated: May 20, 2014