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

The recruitment status of this study is unknown because the information has not been verified recently.

Verified February 2008 by University of Colorado, Denver. Recruitment status was Recruiting

First Received on February 28, 2008. Last Updated on March 6, 2008 History of Changes

Sponsor:	University of Colorado, Denver
Collaborator:	Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00630734

Purpose

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.

Condition	Intervention	Phase
HIV Infections Hyperlipidemia	Drug: Pravastatin, darunavir, ritonavir	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Genetic Predictors of Pharmacokinetic Variability in the Drug-Drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency Help Me Understand Genetics

MedlinePlus related topics: Drug Reactions HIV/AIDS

Drug Information available for: Pravastatin Pravastatin sodium Ritonavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

Change in pravastatin AUC when pravastatin is administered with and without darunavir/ritonavir. [ Time Frame: multiple dose pravastatin (4 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in pravastatin Cmax, tmax, t1/2, and oral clearance when pravastatin is administered with and without darunavir/ritonavir. [ Time Frame: multiple dose pravastatin (4 days) ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	February 2008
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A	Drug: Pravastatin, darunavir, ritonavir Days 1-4: Pravastatin 40 mg QD; Days 5-11: Washout; Days 12-14: Darunavir 600mg/Ritonavir 100mg BID Days 15-18: Darunavir 600mg/Ritonavir 100 mg BID + Pravastatin 40 mg QD

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00630734

Contacts

Contact: Christina L Aquilante, PharmD

303-315-3119

christina.aquilante@uchsc.edu

Locations

United States, Colorado
University of Colorado Denver and Health Sciences Center	Recruiting
Denver, Colorado, United States, 80262
Contact: Christina L Aquilante, PharmD 303-315-3119 christina.aquilante@uchsc.edu
Sub-Investigator: Peter L Anderson, PharmD
Sub-Investigator: Jennifer J Kiser, PharmD
Sub-Investigator: Lisa A Kosmiski, MD
Sub-Investigator: Uwe Christians, PhD

Sponsors and Collaborators

University of Colorado, Denver

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Investigators

Principal Investigator:

Christina L Aquilante, PharmD

University of Colorado Denver and Health Sciences Center

More Information

No publications provided

Responsible Party:	Christina Aquilante, Pharm.D., University of Colorado Denver and Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00630734 History of Changes
Other Study ID Numbers:	COMIRB07-0272, TMC114HIV4003
Study First Received:	February 28, 2008
Last Updated:	March 6, 2008
Health Authority:	United States: Food and Drug Administration; United States: Colorado Multiple Institutional Review Board; United States: University of Colorado General Clinical Research Center

Keywords provided by University of Colorado, Denver:

HIV
Pravastatin
Darunavir
Ritonavir
Genetic

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Hyperlipidemias
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

Pravastatin
Ritonavir
Darunavir
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 12, 2012