Darunavir/Ritonavir and Rosuvastatin Pharmacokinetic Study

NCT00885495 | Completed Phase 1 Results

• 1 other identifier: IDC 40
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

HIV; dyslipidemia; statins; protease inhibitors

Outcome Measures

Primary Outcomes (2)

• Cmax of Rosuvastatin

  7 days

• AUC of Rosuvastatin

  7 days

Secondary Outcomes (2)

• To Investigate the Effect of Rosuvastatin on the Steady State Pharmacokinetics of Darunavir/Ritonavir.

  45 days

• 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.

  45 days

Study Arms (2)

B

ACTIVE COMPARATOR

Darunavir+ritonavir x 7 days; Rosuvastatin x 7 days; Combination x 7 days

Drug: darunavir, ritonavir, rosuvastatin

A

ACTIVE COMPARATOR

Rosuvastatin x 7 days; darunavir+ritonavir x 7 days; Combination x 7 days

Drug: rosuvastatin, darunavir, ritonavir

Interventions

darunavir, ritonavir, rosuvastatin DRUG

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

Also known as: Prezista, Norvir, Crestor

B

rosuvastatin, darunavir, ritonavir DRUG

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

Also known as: Prezista, Norvir, Crestor

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Absence of HIV-1/HIV-2 infection as documented by a licensed ELISA test kit within 21 days prior to study entry.
• Male or female subjects, aged ≥ 18 and ≤ 60 years
• 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.
• Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
• Able to comply with protocol requirements.
• 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.

You may not qualify if:

• 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.
• 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.
• Creatinine clearance of ≤ 60mL/min.
• Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability.
• eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria, that in the opinion of the investigator would represent a contraindication to study enrollment.
• Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the medications administered in the trial.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati AIDS Clinical Trials Unit

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Conditions

HIV Infections; Dyslipidemias

Interventions

Darunavir; Ritonavir; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines

Limitations and Caveats

No clinical outcome data beyond 7 days is available. Cannot necessarily extrapolate directly to persons with HIV.

Results Point of Contact

• Title: Dr. Carl J. Fichtenbaum
• Organization: University of Cincinnati College of Medicine

carl.fichtenbaum@uc.edu

513-584-6361

Study Officials

• Carl J Fichtenbaum, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 20, 2009
• First Posted: April 22, 2009
• Study Start: January 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 11, 2022
• Results First Posted: January 19, 2022

Record last verified: 2022-01

Locations

US (1)