Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David Haas, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00729924
First received: August 4, 2008
Last updated: March 2, 2015
Last verified: March 2015

August 4, 2008
March 2, 2015
August 2008
February 2011   (final data collection date for primary outcome measure)
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
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).
This study will determine if there are associations between a frequent C>T single nucleotide polymorphism (SNP) in the drug transporter gene ABCB1 (also known as MDR1) and penetration of raltegravir (RGV) into cerebrospinal fluid (CSF). [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00729924 on ClinicalTrials.gov Archive Site
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
This outcome was the ratio of the 4-hour CSF concentration value (ng/mL) to the 4-hour plasma concentration value (ng/mL).
Not Provided
Not Provided
Not Provided
 
Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid
Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

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.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier where it limits entry of substrate drugs into the central nervous system. Raltegravir (MK-0158), a new HIV-1 integrase inhibitor and potentially major addition to the therapeutic armamentarium against HIV, is a substrate for P-gp. Studies are warranted to elucidate the relevance of P-gp transport for raltegravir in the central nervous system.

Interventional
Phase 2
Phase 3
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
HIV Infections
Drug: Raltegravir
400mg orally every 12 hours for 7 days
Other Name: MK-0518
Experimental: Open label oral raltegravir
Raltegravir a single 400 mg pill taken orally every 12 hours for a total of 7 days.
Intervention: Drug: Raltegravir
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
August 2011
February 2011   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Able to give informed consent.
  2. Negative HIV-1 serology.
  3. At least 18 but no more than 55 years of age.
  4. Body mass index <30.
  5. Estimated creatinine clearance ≥ 50 mL/minute within 30 days prior to study entry.
  6. 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.
  7. Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days before study entry.
  8. Must agree not to participate in a conception process.
  9. Drug transporter gene ABCB1 position 3435 genotype C/C or T/T.

Exclusion criteria:

  1. Use of any medication that is metabolized by CYP3A or UGT1A1.
  2. Anticipated need to take any medication that is metabolized by CYP3A or UGT1A1 during the study.
  3. Active drug use or dependence.
  4. Inability to abstain from alcohol-containing beverages, grapefruit, and grapefruit juice.
  5. Serious illness that would interfere with study participation.
  6. Hospitalization for any reason or therapy for serious illness within 14 days prior to study entry.
  7. History of hypersensitivity to study drug or its formulation.
  8. 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.
  9. Breast-feeding.
  10. Evidence of CNS infection or space occupying lesion by history or physical examination.
  11. History of significant CNS disorder.
  12. Prisoners or subjects who are compulsorily detained.
  13. ABCB1 position 3435 C/T heterozygosity.
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00729924
080536
No
David Haas, Vanderbilt University
Vanderbilt University
Not Provided
Principal Investigator: David W Haas, MD Vanderbilt University
Vanderbilt University
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP