Darunavir/Ritonavir and Rosuvastatin Pharmacokinetic Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00885495
Recruitment Status : Unknown
Verified April 2009 by University of Cincinnati.
Recruitment status was:  Active, not recruiting
First Posted : April 22, 2009
Last Update Posted : April 22, 2009
Information provided by:
University of Cincinnati

Brief Summary:
This is a phase I, open-label, controlled drug interaction study to determine the effects of darunavir plus ritonavir on the pharmacokinetics of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, in HIV-1-seronegative subjects.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: darunavir, ritonavir, rosuvastatin Drug: rosuvastatin, darunavir, ritonavir Phase 1 Phase 2

Detailed Description:
Twelve HIV-negative healthy volunteers will be randomized to one of two groups. Group 1 would receive rosuvastatin 10mg daily (Treatment A) in interval 1 for 7 days, followed by a washout period of at least 7 days. In interval 2, darunavir/ritonavir 600/100mg bid (Treatment B) would be administered for 7 days, followed by another 7 day washout period. Lastly, in interval 3 subjects will administer darunavir/ritonavir and rosuvastatin (Treatment C) for total of 7 days. Group 2 will administer Treatment B in interval 1 for 7 days, followed by a washout period of 7 days, then treatment A in interval 2 for 7 days followed by another 7 day washout period. Group 2 would then co-administer rosuvastatin and darunavir/ritonavir for the last 7 days. Intensive PK sampling will be performed on day 7, 21 and 35 following a meal.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effects of Darunavir Plus Ritonavir on the Pharmacokinetics and Pharmacodynamics of Rosuvastatin
Study Start Date : January 2009
Estimated Primary Completion Date : June 2009
Estimated Study Completion Date : August 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: B
Darunavir+ritonavir x 7 days; Rosuvastatin x 7 days; Combination x 7 days
Drug: darunavir, ritonavir, rosuvastatin
darunavir 600 mg twice daily for 7 days ritonavir 100 mg twice daily for 7 days rosuvastatin 10 mg once daily for 7 days Combination of all three drugs for 7 days
Other Names:
  • Prezista
  • Norvir
  • Crestor

Active Comparator: A
Rosuvastatin x 7 days; darunavir+ritonavir x 7 days; Combination x 7 days
Drug: rosuvastatin, darunavir, ritonavir
rosuvastatin 10 mg daily for 7 days; darunavir 600 mg twice daily for 7 days with ritonavir 100 mg twice daily for 7 days; Combination of all three for 7 days
Other Names:
  • Prezista
  • Norvir
  • Crestor

Primary Outcome Measures :
  1. To investigate the effect of darunavir/ritonavir on the pharmacokinetics of rosuvastatin. [ Time Frame: 45 days ]

Secondary Outcome Measures :
  1. To investigate the effect of rosuvastatin on the steady state pharmacokinetics of darunavir/ritonavir. [ Time Frame: 45 days ]
  2. To compare the change in low-density lipoprotein (LDL) cholesterol with rosuvastatin therapy alone, darunavir/ritonavir therapy alone and with the co-administration of rosuvastatin and darunavir/ritonavir. [ Time Frame: 45 days ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Absence of HIV-1/HIV-2 infection as documented by a licensed ELISA test kit within 21 days prior to study entry.
  2. Male or female subjects, aged ≥ 18 and ≤ 60 years
  3. Weight ≥50 kg and a Body Mass Index ([BMI], weight in kg divided by the square of height in meters) ≥18.0 and ≤ 35.0 kg/m2. Refer to Appendix I.
  4. Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
  5. Able to comply with protocol requirements.
  6. Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of blood tests and a urinalysis carried out at screening.

Exclusion Criteria:

  1. History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures.
  2. Currently active significant gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease, that in the opinion of the investigator would represent a contraindication to study enrollment.
  3. Creatinine clearance of ≤ 60mL/min.
  4. Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability.
  5. eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria, that in the opinion of the investigator would represent a contraindication to study enrollment.
  6. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the medications administered in the trial.
  7. History of significant drug allergy such as, but not limited to, sulphonamides and penicillins. Prezista is a sulphonamide. The potential for cross-sensitivity between drugs in the sulphonamide class and Prezista in HIV-negative subjects is unknown.
  8. Use of concomitant medication, including investigational, prescription, and over-the-counter products and dietary supplements with the following exceptions: aspirin, acetaminophen, anti-histamines such as diphenhydramine, inhalers for asthma, daily multivitamins, mineral supplements and hormonal oral contraceptives. Concomitant medication other than those listed above must have been discontinued at least 7 days before study entry.
  9. Female subjects of childbearing potential without use of effective nonhormonal birth control methods, or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period; Note: Estrogen-based hormonal contraception may not be reliable when taking Prezista, therefore to be eligible for this trial, women of childbearing potential should either:

    • use a double barrier method to prevent pregnancy (i.e., using a condom with either diaphragm or cervical cap);
    • use non-estrogen hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom);
    • use a intrauterine device in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom);
    • be not sexually active, or have a vasectomized partner (confirmed sterile).

    Women with tubal ligation are required to use one non-hormonal contraceptive method.

    Women who are postmenopausal for at least 2 years, and women with total hysterectomy are considered of non-childbearing potential.

  10. A positive pregnancy test or breast feeding at screening.
  11. Participation in an investigational drug trial within 90 days prior to the first intake of trial medication.
  12. Donation of blood or plasma within 60 days preceding the first trial-related blood drawing.
  13. Subjects with the following laboratory abnormalities at screening as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events ("DAIDS grading table") and in accordance with the normal ranges of the trial clinical laboratory:

    • serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN]);
    • lipase or pancreatic amylase grade 1 or greater (≥ 1.1 x 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),
    • any other laboratory abnormality of grade 2 or above

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00885495

United States, Ohio
University of Cincinnati AIDS Clinical Trials Unit
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
Principal Investigator: Carl J Fichtenbaum, MD University of Cincinnati

Responsible Party: Carl J. Fichtenbaum, MD, University of Cincinnati Identifier: NCT00885495     History of Changes
Other Study ID Numbers: IDC 40
First Posted: April 22, 2009    Key Record Dates
Last Update Posted: April 22, 2009
Last Verified: April 2009

Keywords provided by University of Cincinnati:
protease inhibitors

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Rosuvastatin Calcium
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors