Healthy Participants
Conditions
Keywords
Healthy participants, Rilpivirine, Metformin, Pharmacokinetics
Brief summary
The purpose of the study is to evaluate the effect of steady-state (constant concentration of medication in the blood) rilpivirine on pharmacokinetics (how a single dose of metformin is absorbed in the body, distributed within the body, and removed from the body) of a single dose of metformin, over time, in healthy adult participants.
Detailed description
This is a phase I, open-label (all people know the identity of the intervention) and sequential study (study medication is given in a sequence) in healthy participants, to investigate the pharmacokinetic interaction between steady-state rilpivirine and a single dose of metformin. The study consists of 3 phases including, the screening phase (28 days before enrollment), treatment phase (19 days), and the follow-up phase (7 days after the last intake of study medication). All participants will receive study medications in two sessions in a fixed, sequential order as a session 1 (a single dose of metformin on Day 1) followed by washout period (period when no treatment is received) of 4 days and then session 2 (rilpivirine on Day 5 to Day 17 with a single dose of metformin on Day 15). The duration of the study is approximately 54 days. Safety evaluations including adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination (including skin examination) will be monitored throughout the study.
Interventions
DRUGMetformin
Type=exact number, unit=mg, number=850, form=tablet, route=oral. Participants will receive single dose of metformin on Day 1 and Day 15.
DRUGRilpivirine
Type=exact number, unit=mg, number=25, form=tablet route=oral. Participants will receive 1 tablet of rilpivirine from Day 5 to Day 17.
Sponsors
Janssen R&D Ireland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants should be healthy on the basis of physical examination, medical history, vital signs, electrocardiogram, the results of blood biochemistry and hematology tests and a urinalysis performed at screening * Participant must have a Body Mass Index of 18.5 to 30.0 kg/m2 * Male participants should agree to protocol-defined use of effective contraception and women must be postmenopausal or surgically sterile * Female participants must have a negative pregnancy test at screening * Participants must be non-smoking for at least 3 months prior to screening
Exclusion criteria
* A positive Human immunodeficiency virus (HIV)-1 or HIV-2 test and Hepatitis A, B or C infection at screening * Currently active clinically significant gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrine, renal, hepatic, respiratory, inflammatory or infectious disease with any history of clinically significant skin disease * Any history of tuberculosis, ocular herpes, or uveitis * Have previously participated in more than one study with etravirine - TMC120 (dapivirine) and/or rilpivirine * Participants with abnormal laboratory values at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma analyte concentration (Cmax) of metformin | Day 1 and Day 15 | — |
| Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin | Day 1 and Day 15 | — |
| Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration after dosing (AUClast) of metformin | Day 1 and Day 15 | — |
| AUC extrapolated to infinity of metformin | Day 1 and Day 15 | AUC extrapolated to infinity, calculated as AUClast + Clast/apparent terminal elimination rate constant, where Clast is the last measurable plasma analyte concentration; extrapolations of more than 20 percent of the total AUC are reported as approximations. |
| Apparent terminal elimination rate constant of metformin | Day 1 and Day 15 | Apparent terminal elimination rate constant will be estimated by linear regression using the terminal log-linear phase of the logarithmic transformed conentration versus time data. |
| Apparent terminal elimination half-life of metformin | Day 1 and Day 15 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average steady-state plasma concentration (Css,av) | Day 15 | Css,av is calculated by AUC dosing interval/dosing interval at steady-state |
| Predose plasma analyte concentration (C0h) of rilpivirine | Day 12, Day 13, Day 14, Day 15, Day 17, Day 18 | — |
| Number of participants with adverse events as a measure of safety and tolerability | Up to 54 Days | — |
| Fluctuation index (FI) | Day 15 | FI, percentage fluctuation is variation between maximum and minimum plasma concentration at steady-state |
| Minimum observed plasma analyte concentration (Cmin) of rilpivirine | Day 15 | — |
| Maximum observed plasma analyte concentration (Cmax) of rilpivirine | Day 15 | — |
| Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine | Day 15 | — |
| Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h) | Day 15 | — |
| AUC from time of administration up to 24 hours after administration (AUC24h) | Day 15 | — |
Countries
United States
Outcome results
None listed