Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz

HIV Clinical Trial

Official title:

The Effect of Efavirenz and Ritonavir-boosted Darunavir on the Pharmacokinetics of the HMG CoA Reductase Inhibitor Pitavastatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01695954
• Other study ID #: 11-01787
• Status: Completed
• Phase: Phase 1
• Start date: May 2012
• Est. completion date: January 2013

Study information

• Verified date: July 2020
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV
• Hyperlipidemia
• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

Drug:
• Pitavastatin
Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.
• Darunavir
Darunavir 400 mg tablets x 2 taken daily in Arm B
• Ritonavir
Ritonavir 100 mg tablets taken daily in Arm B
• Efavirenz
Efavirenz 600 mg tablets taken at bedtime in Arm A

Locations

Country	Name	City	State
United States	Bellevue/NYU AIDS Clinical Trials Unit	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
NYU Langone Health	Kowa Pharmaceuticals America, Inc., New York City Health and Hospitals Corporation, University at Buffalo

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC	24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin	0 to 24 hours
Primary	GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin	Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin	0 to 24 hours
Secondary	GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir	Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.	Day 18