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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01719614
First received: October 30, 2012
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Healthy Participants
Drug: Metformin
Drug: Rilpivirine
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Maximum observed plasma analyte concentration (Cmax) of metformin [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
  • Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
  • Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration after dosing (AUClast) of metformin [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
  • AUC extrapolated to infinity of metformin [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Predose plasma analyte concentration (C0h) of rilpivirine [ Time Frame: Day 12, Day 13, Day 14, Day 15, Day 17, Day 18 ] [ Designated as safety issue: No ]
  • Minimum observed plasma analyte concentration (Cmin) of rilpivirine [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Maximum observed plasma analyte concentration (Cmax) of rilpivirine [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h) [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • AUC from time of administration up to 24 hours after administration (AUC24h) [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Average steady-state plasma concentration (Css,av) [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    Css,av is calculated by AUC dosing interval/dosing interval at steady-state

  • Fluctuation index (FI) [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    FI, percentage fluctuation is variation between maximum and minimum plasma concentration at steady-state

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 54 Days ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: October 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rilpivirine+Metformin
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).
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.
Other Name: Metformin
Drug: 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.

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01719614

Locations
United States, Kansas
Overland Park, Kansas, United States
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01719614     History of Changes
Other Study ID Numbers: CR100909, TMC278IFD1004
Study First Received: October 30, 2012
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen R&D Ireland:
Healthy participants
Rilpivirine
Metformin
Pharmacokinetics

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014