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CompletedNCT00729924Updated Mar 3, 2015Results posted

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

A Phase 2/3 interventional study of Raltegravir in HIV Infections, sponsored by Vanderbilt University. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-03-03.

Sponsored by Vanderbilt University · Phase 2/3, Interventional, and Basic science

Phase
Phase 2/3
Study type
Interventional
Enrollment
40
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

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.

02

Conditions studied

  • HIV Infections

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Keywords

  • Raltegravir
  • CSF
  • ABCB1 SNP
  • HIV/AIDS
03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 40 is below the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

Vanderbilt University is the lead sponsor of 508 studies on the registry; 19 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 5 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Open label oral raltegravir

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

    Drug: Raltegravir

Interventions

  • DrugRaltegravir

    400mg orally every 12 hours for 7 days

    Also known as: MK-0518

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What researchers measure

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).

    Time frame: Day 7

Secondary outcomes

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

    This outcome was the ratio of the 4-hour CSF concentration value (ng/mL) to the 4-hour plasma concentration value (ng/mL).

    Time frame: Day 7

07

Results

Posted Mar 3, 2015
Limitations and caveats
There were no limitations to this trial.

Participant flow

Participant flow — Overall Study
MilestoneRaltegravir 400mg Orally Every 12 Hours for 7 Days.
Started40
Completed40
Not completed0

Outcome measures

PrimaryPenetration 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).

Time frame:
Day 7
Reported as:
Median · 1/h
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve.
1/hRaltegravir: 400mg Orally Every 12 Hours for 7 Days (ABCB1 C/CRaltegravir: 400mg Orally Every 12 Hours for 7 Days (ABCB1 T/T
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve.0.0066 (0.0050 to 0.0081)0.0070 (0.0060 to 0.0095)
Statistical analysis
  • Raltegravir: 400mg Orally Every 12 Hours for 7 Days (ABCB1 C/C vs Raltegravir: 400mg Orally Every 12 Hours for 7 Days (ABCB1 T/T · Wilcoxon (Mann-Whitney) · p = 0.43 (The p-value is not adjusted for multiple comparisons.)
SecondaryPenetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint.

This outcome was the ratio of the 4-hour CSF concentration value (ng/mL) to the 4-hour plasma concentration value (ng/mL).

Time frame:
Day 7
Reported as:
Median · ratio
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint.
ratioRaltegravir: 400mg Orally Every 12 Hours for 7 Days: ABCB1 C/CRaltegravir: 400mg Orally Every 12 Hours for 7 Days: ABCB1 T/T
Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint.0.028 (0.014 to 0.057)0.021 (0.016 to 0.045)
Statistical analysis
  • Raltegravir: 400mg Orally Every 12 Hours for 7 Days: ABCB1 C/C vs Raltegravir: 400mg Orally Every 12 Hours for 7 Days: ABCB1 T/T · Wilcoxon (Mann-Whitney) · p = 0.43 (The p-value is not adjusted for multiple comparisons.)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Raltegravir: 400mg Orally Every 12 Hours for 7 Days—0/40 (0%)1/40 (2.5%)
Most frequent other events
Most frequent other events
EventRaltegravir: 400mg Orally Every 12 Hours for 7 Days
post-lumbar puncture headacheNervous system disorders1/40

Baseline characteristics

Age, Continuous
Age, Continuous(years)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
Median34.5 (26.8 to 45)
Sex: Female, Male
Sex: Female, Male(Participants)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
Female20
Male20
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White40
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
United States40
Cerebrospinal Fluid Protein
Cerebrospinal Fluid Protein(mg/dL)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
Median33 (24 to 43)
Weight
Weight(kilograms)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
Median74.6 (62.6 to 80.5)
Body Mass Index
Body Mass Index(kilgrams/(meter squared))Raltegravir: 400mg Orally Every 12 Hours for 7 Days
Median24.0 (22.2 to 25.6)
ABCB1 Genotype
ABCB1 Genotype(participants)Raltegravir: 400mg Orally Every 12 Hours for 7 Days
C/C Genotype20
T/T Genotype20
08

Study locations

1 site
  • Vanderbilt Therapeutics Clinical Research Site
    Nashville, Tennessee 37204, United States
09

References and documents

Publications

  • 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. PubMed 24349334 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 3, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00729924
Lead sponsor
Vanderbilt University
Responsible party
David Haas (Professor of Medicine, Vanderbilt University) — Principal investigator
First posted
Aug 8, 2008
Start date
Aug 2008
Primary completion
Feb 2011
Completion
Aug 2011
Results posted
Mar 3, 2015
Last update
Mar 3, 2015

Study contacts

David W Haas, MD
principal investigator · Vanderbilt University Medical Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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