Back to results

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Raltegravir

About this trial

This is an interventional basic science trial for HIV Infections focused on measuring Raltegravir, CSF, ABCB1 SNP, HIV/AIDS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria:

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.

Exclusion criteria:

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.

Sites / Locations

Vanderbilt Therapeutics Clinical Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open label oral raltegravir

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

Full Information

NCT ID

NCT00729924

First Posted

August 4, 2008

Last Updated

March 2, 2015

Sponsor

Vanderbilt University

1. Study Identification

Unique Protocol Identification Number

NCT00729924

Brief Title

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

Official Title

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Raltegravir, CSF, ABCB1 SNP, HIV/AIDS

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open label oral raltegravir

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Raltegravir

Other Intervention Name(s)

MK-0518

Intervention Description

400mg orally every 12 hours for 7 days

Primary Outcome Measure Information:

Title

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

Description

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 Outcome Measure Information:

Title

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

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: 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. Exclusion criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David W Haas, MD

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt Therapeutics Clinical Research Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37204

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24349334

Citation

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.

Results Reference

result

Learn more about this trial

Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

We'll reach out to this number within 24 hrs