Clinical trial NCT01719614: A Study to Explore Pharmacokinetic Interaction Between Rilpivirine and Metformin in Healthy Participants
Official title: A Phase I, Open-Label Study in Healthy Subjects to Explore the Potential for a Pharmacokinetic Interaction Between Steady-State Rilpivirine and a Single Dose Of Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy participants
Rilpivirine
Metformin
Pharmacokinetics
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2012-11-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed plasma analyte concentration (Cmax) of metformin
timeFrame: Day 1 and Day 15
measure: Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin
timeFrame: Day 1 and Day 15
measure: Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration after dosing (AUClast) of metformin
timeFrame: Day 1 and Day 15
measure: AUC extrapolated to infinity of metformin
timeFrame: Day 1 and Day 15
measure: Apparent terminal elimination rate constant of metformin
timeFrame: Day 1 and Day 15
measure: Apparent terminal elimination half-life of metformin
timeFrame: Day 1 and Day 15
Secondary outcomes:
measure: Predose plasma analyte concentration (C0h) of rilpivirine
timeFrame: Day 12, Day 13, Day 14, Day 15, Day 17, Day 18
measure: Minimum observed plasma analyte concentration (Cmin) of rilpivirine
timeFrame: Day 15
measure: Maximum observed plasma analyte concentration (Cmax) of rilpivirine
timeFrame: Day 15
measure: Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine
timeFrame: Day 15
measure: Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h)
timeFrame: Day 15
measure: AUC from time of administration up to 24 hours after administration (AUC24h)
timeFrame: Day 15
measure: Average steady-state plasma concentration (Css,av)
timeFrame: Day 15
measure: Fluctuation index (FI)
timeFrame: Day 15
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 54 Days
Other outcomes:
Locations:
city: Overland Park
country: United States
state: Kansas
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References: