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

• 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 ]
  

• 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 ]
  

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.