Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

NCT ID: NCT00729924

Last Updated: 2015-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2011-08-31

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.

Conditions

HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Open label oral raltegravir

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

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: DRUG

400mg orally every 12 hours for 7 days

Interventions

Raltegravir

400mg orally every 12 hours for 7 days

Intervention Type: DRUG

Other Intervention Names

MK-0518

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

David Haas

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David W Haas, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt Therapeutics Clinical Research Site

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24349334 (View on PubMed)

Other Identifiers

080536

Identifier Type: -

Identifier Source: org_study_id