Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz

NCT ID: NCT01695954

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2013-01-31

Brief Summary

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.

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.

Conditions

Hyperlipidemia; HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Arm A

Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.

Group Type: EXPERIMENTAL

Pitavastatin

Intervention Type: DRUG

Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.

Efavirenz

Intervention Type: DRUG

Efavirenz 600 mg tablets taken at bedtime in Arm A

Arm B

Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.

Group Type: EXPERIMENTAL

Pitavastatin

Intervention Type: DRUG

Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.

Darunavir

Intervention Type: DRUG

Darunavir 400 mg tablets x 2 taken daily in Arm B

Ritonavir

Intervention Type: DRUG

Ritonavir 100 mg tablets taken daily in Arm B

Interventions

Pitavastatin

Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.

Intervention Type: DRUG

Darunavir

Darunavir 400 mg tablets x 2 taken daily in Arm B

Intervention Type: DRUG

Ritonavir

Ritonavir 100 mg tablets taken daily in Arm B

Intervention Type: DRUG

Efavirenz

Efavirenz 600 mg tablets taken at bedtime in Arm A

Intervention Type: DRUG

Other Intervention Names

Livalo; Prezista; Norvir; Sustiva

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

New York City Health and Hospitals Corporation

OTHER

Sponsor Role: collaborator

Kowa Pharmaceuticals America, Inc.

INDUSTRY

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Aberg, M.D.

Role: PRINCIPAL_INVESTIGATOR

NYU School of Medicine

Locations

Bellevue/NYU AIDS Clinical Trials Unit

New York, New York, United States

Countries

United States

References

Malvestutto CD, Ma Q, Morse GD, Underberg JA, Aberg JA. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):390-6. doi: 10.1097/QAI.0000000000000333.

Reference Type: RESULT

PMID: 25202920 (View on PubMed)

Other Identifiers

11-01787

Identifier Type: -

Identifier Source: org_study_id