The Rilpivirine Cerebrospinal-fluid (CSF) Study

Condition(s) targeted: HIV

Intervention: Rilpivirine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Imperial College London

Official(s) and/or principal investigator(s):
Alan Winston, MBChB MD, Principal Investigator, Affiliation: Imperial College London

This is a phase I pharmacokinetic study of HIV positive patients stable on antiretroviral therapy who will switch treatment when enrolled from nevirapine to rilpivirine. On day 60 of the study the participants will attend clinic where they will have blood collected followed by a lumbar puncture where cerebrospinal fluid will be collected to measure drug concentration. The participants will then restart their original regime with nevirapine.

Official title: A Phase I Pharmacokinetic Study to Assess the Cerebrospinal-fluid (CSF) Exposure of Rilpivirine in HIV-infected Subjects Switching From TDF/FTC/Nevirapine to TDF/FTC/Rilpivirine

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: CSF:Plasma Ratio of Rilpivirine Levels

Secondary outcome: Number of Subjects With HIV Viral Load Above 50 Copies Per mL

Detailed description: To investigate the following parameters in HIV-infected patients switching antiretroviral therapy from TDF/FTC/nevirapine to TDF/FTC/rilpivirine for 60 days:

- CSF exposure and CSF : plasma ratio of rilpivirine

- Safety and tolerability of switching antiretroviral therapy from TDF/FTC/nevirapine to

TDF/FTC/rilpivirine

- Changes in cerebral metabolites measured via 1-H MRS after switching antiretroviral

therapy to TDF/FTC/rilpivirine

- Seminal fluid exposure of rilpivirine

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- HIV-1 infected males subjects

- signed informed consent

- willing to switch therapy as per study protocol

- no previous exposure to rilpivirine

- plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over

the last 3 months

- currently receiving a stable antiretroviral regimen comprising of TDF/FTC with

nevirapine with nevirapine dosed either 200 mg twice daily or 400 mg once daily with no antiretroviral drug switches for at least 3 months

- no clinically-significant resistance documented on any prior HIV-1 genotypic

resistance testing

- subjects in good health upon medical history, physical exam, and laboratory testing

- BMI above or equal to 18 and below 32

- Male subjects who are heterosexually active must use two forms of barrier

contraception (e. g., condom and diaphragm) during heterosexual intercourse, from screening through completion of the study.

- Have local screening laboratory results (haematology and chemistry that fall within

the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance

- No contraindications to having a lumbar puncture examination found on MRI of the

brain Exclusion Criteria:

- current alcohol abuse or drug dependence

- positive urine drug of abuse screening

- active opportunistic infection or significant co-morbidities

- current disallowed concomitant medication (as listed in section 4. 1.3)

- contraindication to MR examination or lumbar puncture examination

- recent head injury (in last 30 days) or chronic ongoing neurological diseases

Imperial College Healthcare NHS Trust, London W2 1NY, United Kingdom

Starting date: March 2012
Last updated: May 19, 2014