Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

NCT00729924 | Completed Phase 2 Results

• 1 other identifier: 080536
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to find out how much of the drug raltegravir (RGV) gets into cerebrospinal fluid (CSF), compared to how much get into the blood and to find out if normal changes in a certain gene in your body affects how much RGV gets into the CSF.

Conditions

HIV Infections

Keywords

Raltegravir; CSF; ABCB1 SNP; HIV/AIDS

Outcome Measures

Primary Outcomes (1)

• Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve.

  The primary outcome for this study was the ratio of the 4-hour CSF concentration value (ng/mL) to the partial plasma area-under-the-curve 0-4h value (h\*ng/mL).

  Day 7

Secondary Outcomes (1)

• Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint.

  Day 7

Study Arms (1)

Open label oral raltegravir

EXPERIMENTAL

Raltegravir a single 400 mg pill taken orally every 12 hours for a total of 7 days.

Drug: Raltegravir

Interventions

Raltegravir DRUG

400mg orally every 12 hours for 7 days

Also known as: MK-0518

Open label oral raltegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give informed consent.
• Negative HIV-1 serology.
• At least 18 but no more than 55 years of age.
• Body mass index \<30.
• Estimated creatinine clearance ≥ 50 mL/minute within 30 days prior to study entry.
• Within 30 days prior to study entry:
• Absolute neutrophil count ≥ 1,000/mm3.
• Hemoglobin ≥ 12.5 g/dL for males and ≥ 11.5 g/dL for females.
• Platelet count ≥ 100,000/mm3.
• AST, ALT, and total bilirubin within normal range.
• Alkaline phosphatase \< or = 1.5 x upper limit of normal.
• Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days before study entry.
• Must agree not to participate in a conception process.
• Drug transporter gene ABCB1 position 3435 genotype C/C or T/T.

You may not qualify if:

• Use of any medication that is metabolized by CYP3A or UGT1A1.
• Anticipated need to take any medication that is metabolized by CYP3A or UGT1A1 during the study.
• Active drug use or dependence.
• Inability to abstain from alcohol-containing beverages, grapefruit, and grapefruit juice.
• Serious illness that would interfere with study participation.
• Hospitalization for any reason or therapy for serious illness within 14 days prior to study entry.
• History of hypersensitivity to study drug or its formulation.
• As determined by the investigator, a significant active or previous history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s). This is inclusive of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, any chronic gastrointestinal conditions that may affect drug absorption, etc.
• Breast-feeding.
• Evidence of CNS infection or space occupying lesion by history or physical examination.
• History of significant CNS disorder.
• Prisoners or subjects who are compulsorily detained.
• ABCB1 position 3435 C/T heterozygosity.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Therapeutics Clinical Research Site

Nashville, Tennessee, 37204, United States

Location

Related Publications (1)

• Johnson DH, Sutherland D, Acosta EP, Erdem H, Richardson D, Haas DW. Genetic and non-genetic determinants of raltegravir penetration into cerebrospinal fluid: a single arm pharmacokinetic study. PLoS One. 2013 Dec 11;8(12):e82672. doi: 10.1371/journal.pone.0082672. eCollection 2013.

  PMID: 24349334 RESULT

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

There were no limitations to this trial.

Results Point of Contact

• Title: David W. Haas, MD
• Organization: Vanderbilt University

david.w.haas@vanderbilt.edu

615-936-8594

Study Officials

• David W Haas, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 4, 2008
• First Posted: August 8, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: August 1, 2011
• Last Updated: March 3, 2015
• Results First Posted: March 3, 2015

Record last verified: 2015-03

Locations

US (1)