Phase 4
Completed N=32
Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
Source: ClinicalTrials.gov NCT00630734 ↗Enrolled (actual)
32
Serious AEs
1.1%
Results posted
Nov 2012
Primary outcomePrimary: Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval — 1.09; 1.59; 1.75 ng*hr/ml — p=0.43
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval |
1.09; 1.59; 1.75 | 0.43 |
| PRIMARY Relative Change in Pravastatin Maximum Plasma Concentration (Cmax) |
1.11; 1.69; 2.32 | 0.28 |
| SECONDARY Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval |
63; 86.6; 123.4 | 0.22 |
| SECONDARY Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax) |
27.7; 33.3; 46.2 | 0.67 |
| SECONDARY Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval |
68.4; 106.8; 145.7 | 0.006 sig |
| SECONDARY Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax) |
30.1; 42.4; 52.8 | 0.08 |
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
Data sourced from ClinicalTrials.gov (NCT00630734). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.