Darunavir/Ritonavir and Rosuvastatin Pharmacokinetic Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by University of Cincinnati.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Cincinnati
ClinicalTrials.gov Identifier:
NCT00885495
First received: April 20, 2009
Last updated: April 21, 2009
Last verified: April 2009
  Purpose

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 Intervention Phase
HIV Infections
Drug: darunavir, ritonavir, rosuvastatin
Drug: rosuvastatin, darunavir, ritonavir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Darunavir Plus Ritonavir on the Pharmacokinetics and Pharmacodynamics of Rosuvastatin

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • To investigate the effect of darunavir/ritonavir on the pharmacokinetics of rosuvastatin. [ Time Frame: 45 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate the effect of rosuvastatin on the steady state pharmacokinetics of darunavir/ritonavir. [ Time Frame: 45 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: January 2009
Estimated Study Completion Date: August 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00885495

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

No publications provided

Responsible Party: Carl J. Fichtenbaum, MD, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00885495     History of Changes
Other Study ID Numbers: IDC 40
Study First Received: April 20, 2009
Last Updated: April 21, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Cincinnati:
HIV
dyslipidemia
statins
protease inhibitors

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Rosuvastatin
Ritonavir
Darunavir
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014