The Rilpivirine Cerebrospinal-fluid (CSF) Study

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Rilpivirine

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rilpivirine and Truvada; TDF/FTC (Truvada™) one tablet once plus Rilpivirine 25 mg daily	Drug: Rilpivirine; Rilpivirine 26mg; Other Names: Edurant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF:Plasma Ratio of Rilpivirine Levels	The levels of rilpivirine will be measured in the cerebral spinal fluid and plasma after 60 days of exposure	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With HIV Viral Load Above 50 Copies Per mL	Plasma viral load will be measured at all study visits to assess if viral load is above the lower limit of detection (50 copies mL)	Day 3,14, 28, 60, 80-100

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Principal Investigator: Alan Winston, MBChB MD, Imperial College London

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: March 22, 2012
• First Submitted That Met QC Criteria: March 23, 2012
• First Posted (Estimate): March 26, 2012

Study Record Updates

• Last Update Posted (Estimate): June 19, 2014
• Last Update Submitted That Met QC Criteria: May 19, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Rilpivirine CSF pharmacokinetics
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Rilpivirine
• Other Study ID Numbers: 278_CSF; 2011-004026-98 (EudraCT Number)