A Study to Explore Pharmacokinetic Interaction Between Rilpivirine and Metformin in Healthy Participants

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01719614
• Other study ID #: CR100909
• Secondary ID: TMC278IFD1004
• Status: Completed
• Phase: Phase 1
• First received: October 30, 2012
• Last updated: March 5, 2014
• Start date: October 2012
• Est. completion date: January 2013

Study information

• Verified date: March 2014
• Source: Janssen R&D Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Metformin
Type=exact number, unit=mg, number=850, form=tablet, route=oral. Participants will receive single dose of metformin on Day 1 and Day 15.
• Rilpivirine
Type=exact number, unit=mg, number=25, form=tablet route=oral. Participants will receive 1 tablet of rilpivirine from Day 5 to Day 17.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen R&D Ireland

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma analyte concentration (Cmax) of metformin		Day 1 and Day 15	No
Primary	Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin		Day 1 and Day 15	No
Primary	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	No
Primary	AUC extrapolated to infinity of metformin	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.	Day 1 and Day 15	No
Primary	Apparent terminal elimination rate constant of metformin	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.	Day 1 and Day 15	No
Primary	Apparent terminal elimination half-life of metformin		Day 1 and Day 15	No
Secondary	Predose plasma analyte concentration (C0h) of rilpivirine		Day 12, Day 13, Day 14, Day 15, Day 17, Day 18	No
Secondary	Minimum observed plasma analyte concentration (Cmin) of rilpivirine		Day 15	No
Secondary	Maximum observed plasma analyte concentration (Cmax) of rilpivirine		Day 15	No
Secondary	Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine		Day 15	No
Secondary	Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h)		Day 15	No
Secondary	AUC from time of administration up to 24 hours after administration (AUC24h)		Day 15	No
Secondary	Average steady-state plasma concentration (Css,av)	Css,av is calculated by AUC dosing interval/dosing interval at steady-state	Day 15	No
Secondary	Fluctuation index (FI)	FI, percentage fluctuation is variation between maximum and minimum plasma concentration at steady-state	Day 15	No
Secondary	Number of participants with adverse events as a measure of safety and tolerability		Up to 54 Days	Yes