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

This study is currently recruiting participants.

Verified by University of Colorado at Denver and Health Sciences Center, February 2008

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

Sponsor:	University of Colorado at Denver and Health Sciences Center
Collaborator:	Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:	University of Colorado at Denver and Health Sciences Center
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:	Treatment, Non-Randomized, Open Label, Crossover Assignment, Pharmacokinetics Study
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:

MedlinePlus related topics: 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 at Denver and Health Sciences Center:

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
A: Experimental	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 at Denver and Health Sciences Center

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:	University of Colorado Denver and Health Sciences Center ( Christina Aquilante, Pharm.D. )
Study ID Numbers:	COMIRB07-0272, TMC114HIV4003
Study First Received:	February 28, 2008
Last Updated:	March 6, 2008
ClinicalTrials.gov Identifier:	NCT00630734 History of Changes
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 at Denver and Health Sciences Center:

HIV
Pravastatin
Darunavir
Ritonavir
Genetic

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Darunavir
Pravastatin
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Dyslipidemias
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents

Hyperlipidemias
Metabolic Diseases
Immune System Diseases
Antilipemic Agents
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir

ClinicalTrials.gov processed this record on November 27, 2009