The Rilpivirine Cerebrospinal-fluid (CSF) Study

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01562886
• Other study ID #: 278_CSF
• Secondary ID: 2011-004026-98
• Status: Completed
• Phase: Phase 1
• First received: March 22, 2012
• Last updated: May 19, 2014
• Start date: March 2012
• Est. completion date: February 2013

Study information

• Verified date: May 2014
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Rilpivirine
Rilpivirine 26mg

Locations

Country	Name	City	State
United Kingdom	Imperial College Healthcare NHS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Janssen-Cilag Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes