HIV
Conditions
Keywords
Rilpivirine CSF pharmacokinetics
Brief 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.
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
Interventions
DRUGRilpivirine
Rilpivirine 26mg
Sponsors
Janssen-Cilag Ltd.
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CSF:Plasma Ratio of Rilpivirine Levels | Day 60 | The levels of rilpivirine will be measured in the cerebral spinal fluid and plasma after 60 days of exposure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With HIV Viral Load Above 50 Copies Per mL | Day 3,14, 28, 60, 80-100 | 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) |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rilpivirine and Truvada TDF/FTC (Truvada™) one tablet once plus Rilpivirine 25 mg daily | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Rilpivirine and Truvada |
|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 9.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United Kingdom | 13 participants |
| Rilpivirine CSF concentration | 0.8 ng/mL |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
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
Time frame: Day 60
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rilpivirine and Truvada | CSF:Plasma Ratio of Rilpivirine Levels | 1.4 ratio expressed as a percentage |
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)
Time frame: Day 3,14, 28, 60, 80-100
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rilpivirine and Truvada | Number of Subjects With HIV Viral Load Above 50 Copies Per mL | 2 participants |