Pharmacokinetic (PK) Study of Single-dose Rosuvastatin and Tipranavir/Ritonavir in Healthy Subjects

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by Johns Hopkins University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00344123
First received: June 22, 2006
Last updated: June 30, 2011
Last verified: June 2008
  Purpose

Tipranavir (TPV) plus ritonavir (RTV) is indicated for use as part of an antiretroviral treatment regimen for resistant HIV-1 infection in adult patients. Since significant cholesterol and triglyceride elevations are commonly reported during TPV/RTV treatment, effective treatment strategies are critical to prevent long-term cardiovascular events. Rosuvastatin, a potent HMG-CoA reductase inhibitor, is unlikely to interact with TPV/RTV since it is not extensively metabolized, however, a formal drug interaction study is needed before this combination can be recommended. This study will examine the pharmacokinetic interactions between tipranavir/ritonavir (TPV/RTV [TPV/r] 500 mg/200 mg twice daily [B.I.D]) and single dose rosuvastatin when the two are co-administered to healthy adult volunteers. The investigators hypothesize that if tipranavir 500 mg is co-administered with low-dose ritonavir 200 mg and rosuvastatin (10 mg) no significant clinical interaction will occur.


Condition Intervention Phase
HIV Infections
Drug: Tipranavir
Drug: Ritonavir
Drug: Rosuvastatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Evaluation of Single-dose Rosuvastatin 10 mg When Co-administered With Steady-state Tipranavir 500 mg/Ritonavir 200 mg TPV/r) B.I.D. in Healthy Adult Volunteers

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • To compare single dose rosuvastatin AUC0-24h and Cmax with single dose rosuvastatin AUC0-24h and Cmax when co-administered with TPV/r 500 mg/200 mg twice daily at steady state

Secondary Outcome Measures:
  • To compare single dose rosuvastatin Cp 24h/C last with single dose rosuvastatin Cp 24h/C last when co-administered with TPV/r 500 mg/200 mg twice daily at steady state
  • To compare the steady state pharmacokinetics (AUC0-12h, Cmax, Cp 12h/C last) of TPV and RTV (TPV 500 mg/RTV 200 mg B.I.D) with steady state pharmacokinetics of TPV and RTV when co-administered with single dose rosuvastatin (10 mg)
  • To evaluate the short term safety and tolerance of TPV/r (500 mg/200 mg B.I.D) combined with single dose rosuvastatin (10 mg)

Estimated Enrollment: 23
Study Start Date: February 2007
Detailed Description:

This is a prospective, open-label pharmacokinetic study in healthy HIV seronegative adults. This study will examine the pharmacokinetic interactions between steady-state TPV/r 500 mg/200 mg B.I.D. and single dose rosuvastatin 10 mg when the drugs are co-administered.

Rosuvastatin 24 hour pharmacokinetic sampling will be performed on days 1-2 and 12-13. Rosuvastatin 48 hr samples will be collected on days 3 and day 14.

Tipranavir and ritonavir 12 hour pharmacokinetic sampling will be on day 11 and 12.

Safety assessments (physical examination, vital sign measurements, and clinical laboratory tests) will be performed at screening, during the study and prior to discharge. Subjects will be continuously monitored for adverse events throughout the duration of the study.

On Day 1, subjects will receive a single 10 mg dose of rosuvastatin. Beginning on Day 3, subjects will receive a combination of TPV 500 mg/RTV 200 mg twice daily for 11 days (Days 3-13).

On Day 12, subjects will receive a single 10 mg dose of rosuvastatin co-administered with TPV/r.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must have a body mass index (BMI) of 18 to 30 kg/m2, inclusive (BMI = weight (kg)/[height (m)]2) and weigh at least 50 kg.
  • Males or females, ages > 18 to < 65 years.
  • Women of childbearing potential (WOCBP) must not be nursing or pregnant. All women of childbearing potential (have not reached menopause nor undergone hysterectomy, bilateral oophorectomy, or tubal ligation) must have a negative serum beta-HCG test performed at screening (within 24 hours before the start of study day 1). Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (hysterectomy, oophorectomy, tubal ligation, or vasectomy) and azoospermia by patient-reported history is acceptable. Both male and female study volunteers of reproductive potential must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate via sperm donation or in vitro fertilization), and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use a form of contraception as specified below while receiving protocol-specified medication(s) and for one month after stopping the medication(s). Male study volunteers will be required to use a barrier method for at least 3 months after completion of the study.

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide

Exclusion Criteria:

  • History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
  • History of acute or chronic pancreatitis.
  • History of diabetes mellitus, hypertriglyceridemia, or chronic renal insufficiency.
  • Proven or suspected acute hepatitis at the time of study entry.
  • Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.
  • Any major surgery within 4 weeks of enrollment. Any gastrointestinal surgery that could impact upon the absorption of study drug.
  • Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment.
  • Inability to tolerate oral medication.
  • Inability to tolerate venipuncture and/or absence of secure venous access.
  • Known or suspected HIV infection or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Known active drug or alcohol abuse which, in the opinion of the investigator, makes study participation to completion unlikely.
  • Any other sound medical, psychiatric, and/or social reason, as determined by the investigator.
  • Subjects with AST, ALT, or bilirubin above the upper limit of normal.
  • Hemoglobin < 9.5 g/dL, and platelet count < 100,000/mm3.
  • Subjects with creatine phosphokinase (CPK) elevation greater than 3 times the upper limit of normal.
  • Any other clinically significant screening lab abnormality (as determined by the investigator)
  • History of any significant drug allergy, drug rash, or sensitivity to any class of drugs relevant to the study drugs.
  • Prior exposure to tipranavir/ritonavir.
  • Exposure to any investigational drug within 4 weeks of enrollment and throughout the study.
  • Any previous hypersensitivity or intolerance to tipranavir or ritonavir or any other ingredient of Aptivus or Norvir.
  • Hypersensitivity to sulfonamides
  • Any previous hypersensitivity or intolerance to rosuvastatin or any other ingredient of Crestor (rosuvastatin).
  • Known elevated liver enzymes in past clinical trials with any compound
  • Use of any agent, within 2 weeks of dosing, that is known to induce or inhibit drug metabolizing enzymes
  • Use of any over-the-counter drugs, including antacids, alternative herbal products, or prescription drugs that, in the opinion of the investigator, might interfere with the absorption, distribution, or metabolism of TPV, RTV, or rosuvastatin within 14 days of study entry.
  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: NCT00344123

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Boehringer Ingelheim
Investigators
Principal Investigator: Paul Pham, PharmD Johns Hopkins University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00344123     History of Changes
Other Study ID Numbers: NA_00003633
Study First Received: June 22, 2006
Last Updated: June 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
HIV

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
Ritonavir
Tipranavir
Rosuvastatin
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 27, 2014