Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bellevue/NYU AIDS Clinical Trials Unit
Kowa Pharmaceuticals America, Inc.
University at Buffalo
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01695954
First received: September 26, 2012
Last updated: September 27, 2012
Last verified: September 2012
  Purpose

The main goal of this study is to determine how taking efavirenz affects the levels of pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are taken together and to see how taking pitavastatin affects the levels in the blood of darunavir.


Condition Intervention Phase
Hyperlipidemia
HIV
Drug: Pitavastatin
Drug: Darunavir
Drug: Ritonavir
Drug: Efavirenz
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: THE EFFECT OF EFAVIRENZ AND RITONAVIR-BOOSTED DARUNAVIR ON THE PHARMACOKINETICS OF THE HMG CoA REDUCTASE INHIBITOR PITAVASTATIN

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • AUC of pitavastatin after coadministration of efavirenz. AUC of pitavastatin after coadministration of darunavir with ritonavir. AUC of efavirenz after coadministration of pitavastatin. AUC of darunavir after coadministration of pitavastatin. [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    24-hour area under the curve (AUC)


Secondary Outcome Measures:
  • Other pharmacokinetic parameters of pitavastatin and efavirenz and of pitavastatin and darunavir+ritonavir. Lipid measurements at days 0,4,14 and 18. [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
    • Other pharmacokinetic parameters of pitavastatin and efavirenz such as Cmax, Cmin, Tmax, and T1/2.
    • Other pharmacokinetic parameters of pitavastatin and darunavir+ritonavir such as Cmax, Cmin, Tmax, and T1/2.
    • At days 0, 4, 14 and 18: Fasting HDL, total cholesterol, LDL and triglycerides for patients in Arm A.
    • At days 0, 4, 14 and 18: Fasting HDL, total cholesterol, LDL and triglycerides for patients in Arm B.


Enrollment: 28
Study Start Date: May 2012
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: (Pitavastatin and Efavirenz)
Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.
Drug: Pitavastatin
Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.
Other Name: Livalo
Drug: Efavirenz
Efavirenz 600 mg tablets taken at bedtime in Arm A
Other Name: Sustiva
Experimental: Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)
Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
Drug: Pitavastatin
Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.
Other Name: Livalo
Drug: Darunavir
Darunavir 400 mg tablets x 2 taken daily in Arm B
Other Name: Prezista
Drug: Ritonavir
Ritonavir 100 mg tablets taken daily in Arm B
Other Name: Norvir

  Hide Detailed Description

Detailed Description:

HIV infected persons are at risk for coronary heart disease due to chronic inflammation associated with the virus itself, the side effects of the antiretroviral (ARV) therapies which can cause elevated cholesterol, and the risk factors such as smoking, high blood pressure and family history of heart disease.

The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol in patients infected with HIV, guidelines recommend the use of statins (a class of lipid lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food and Drug Administration (FDA) for the treatment of high cholesterol.

In order to be able to use pitavastatin safely in HIV-infected patients taking either darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these drugs in the bloodstream.

Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in Arm B.

Arm A:

Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking one efavirenz 600 mg tablet at bedtime.

On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.

On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.

Arm B:

Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4 participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood draw for a final blood draw. They will then stop taking pitavastatin. Participants will then start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.

On day 14, participants will come in for a second 14-hour visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir 400 mg tablets and one ritonavir 100 mg tablet.

On day 18, participants will come in for a third 14-hour PK visit and will have about 9 tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final blood draw. They will then stop taking all study drugs and will either come in or receive a final phone call on day 25.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Absence of HIV-1 infection as documented by any licensed ELISA test kit within 21 days prior to study entry.
  • Male or female aged 18-60 years.
  • Able and willing to provide informed consent.
  • All men and women of reproductive potential must practice adequate birth control to prevent pregnancy from start of the study until completion of the study.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.
  • Hemoglobin > 12.5 g/dL for men; > 11.5 g/dL for women;
  • Absolute neutrophil count >1,500 cells/mm3;
  • Platelet count > 100,000 platelets/mm3;
  • AST (SGOT)/ALT (SGPT) <1.5X ULN;
  • Creatinine <1.5 X ULN
  • Subject is within 20% (+/-) of ideal body weight and must weigh at least 50 kg

Exclusion Criteria:

  • Use of illicit drugs or alcohol which would interfere with the completion of this study.
  • Pregnancy or breast-feeding.
  • History of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, or any chronic gastrointestinal conditions which might interfere with drug absorption.
  • Any medical condition which, in the opinion of the investigator, would interfere with the subjects ability to participate in this protocol.
  • Use of prohibited protocol-specified drugs, prescription or over-the-counter within 14 days prior to study entry.
  • Participation in any investigational drug studies within 30 days prior to 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: NCT01695954

Locations
United States, New York
Bellevue/NYU AIDS Clinical Trials Unit
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Bellevue/NYU AIDS Clinical Trials Unit
Kowa Pharmaceuticals America, Inc.
University at Buffalo
Investigators
Principal Investigator: Judith Aberg, M.D. NYU School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01695954     History of Changes
Other Study ID Numbers: NYU 11-01787
Study First Received: September 26, 2012
Last Updated: September 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
HIV
Hyperlipidemia
Pharmacokinetics
Statins
Darunavir
Efavirenz
Pitavastatin

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Ritonavir
Darunavir
Efavirenz
Pitavastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014