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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00630734
• Other study ID #: 07-0272
• Secondary ID: TMC114HIV4003
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2008
• Last updated: May 20, 2014
• Start date: February 2008
• Est. completion date: September 2010

Study information

• Verified date: May 2014
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2010
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• HIV Infections
• Hyperlipidemia
• Hyperlipidemias

Intervention

Drug:
• Pravastatin
Pravastatin 40 mg by mouth daily on days 1-4
• Darunavir
Darunavir 600mg by mouth twice daily on days 12-18
• Ritonavir
Ritonavir 100mg by mouth twice daily on days 12-18
• Pravastatin
Pravastatin 40 mg by mouth daily on days 15-18

Other:
• Washout
Washout (no medication) on days 5-11.

Locations

Country	Name	City	State
United States	University of Colorado Denver	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval	AUC of darunavir over a 12-hour dosing interval.	0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose	No
Other	Darunavir Maximum Plasma Concentration (Cmax)	Cmax of darunavir over a 12-hour dosing interval	0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose	No
Other	Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval	AUC of ritonavir over a 12-hour dosing interval.	0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose	No
Other	Ritonavir Maximum Plasma Concentration (Cmax)	Cmax of ritonavir over a 12-hour dosing interval	0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose	No
Primary	Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval	AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No
Primary	Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)	Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No
Secondary	Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval	Dosing interval of 24 hours	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No
Secondary	Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)		0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No
Secondary	Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval	Dosing interval of 24 hours	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No
Secondary	Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)		0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose	No