Clinical trial NCT00630734: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Hyperlipidemia
Keywords: HIV
Pravastatin
Darunavir
Ritonavir
Genetic
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
First posted: 2008-03-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
measure: Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Secondary outcomes:
measure: Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
measure: Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
measure: Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
measure: Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Other outcomes:
measure: Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
measure: Darunavir Maximum Plasma Concentration (Cmax)
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
measure: Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
measure: Ritonavir Maximum Plasma Concentration (Cmax)
timeFrame: 0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Christina L Aquilante, PharmD
role: PRINCIPAL_INVESTIGATOR
References: