Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz

NCT01695954 | Completed Phase 1 Results DMC

• 1 other identifier: 11-01787
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperlipidemia; HIV

Keywords

HIV; Hyperlipidemia; Pharmacokinetics; Statins; Darunavir; Efavirenz; Pitavastatin

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir

  Day 18

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: Pitavastatin; Drug: Efavirenz

Arm B

EXPERIMENTAL

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

Drug: Pitavastatin; Drug: Darunavir; Drug: Ritonavir

Interventions

Pitavastatin DRUG

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

Also known as: Livalo

Arm A; Arm B

Darunavir DRUG

Darunavir 400 mg tablets x 2 taken daily in Arm B

Also known as: Prezista

Arm B

Ritonavir DRUG

Ritonavir 100 mg tablets taken daily in Arm B

Also known as: Norvir

Arm B

Efavirenz DRUG

Efavirenz 600 mg tablets taken at bedtime in Arm A

Also known as: Sustiva

Arm A

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NYU Langone Health: lead
• New York City Health and Hospitals Corporation: collaborator
• Kowa Pharmaceuticals America, Inc.: collaborator
• University at Buffalo: collaborator

Study Sites (1)

Bellevue/NYU AIDS Clinical Trials Unit

New York, New York, 10016, United States

Location

Related 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.

  PMID: 25202920 RESULT

MeSH Terms

Conditions

Hyperlipidemias

Interventions

pitavastatin; Darunavir; Ritonavir; efavirenz

Condition Hierarchy (Ancestors)

Dyslipidemias; 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

Limitations and Caveats

Pitavastatin levels for 4 subjects enrolled in Arm B were lost due to emergency transfer of specimens to temporary storage facility during Hurricane Sandy.

Results Point of Contact

• Title: Carlos Malvestutto, MD, MPH
• Organization: NYU School of Medicine

carlos.malvestutto@nyumc.org

212-263-3570

Study Officials

• Judith Aberg, M.D.

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: August 11, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-07

Locations

US (1)