TMC278-TiDP6-C136: Effect of TMC278 on Ethinylestradiol and Norethindrone in Healthy Women.
Condition: HIV; AIDS; Oral Contraceptive
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the pharmacokinetic interaction between the
      combination of ethinylestradiol and norethindrone and TMC278 25 mg once daily.
      Pharmacokinetics means how the drug is absorbed into the bloodstream, distributed in the body
      and eliminated from the body. Furthermore the short-term safety and tolerability (how well
      the body tolerates the drug) of co-administration of TMC278 and ethinylestradiol and
      norethindrone, in healthy women, will be assessed.
    

Detailed description: 
      Human immunodeficiency virus (HIV)-infected patients are routinely being treated with
      combinations of 3 or 4 drugs (highly active antiretroviral therapy [HAART]), to reduce the
      risk of viral resistance development. Development of new potent antiretroviral (ARV) drugs is
      urgently needed to prolong suppression of viral replication in patients infected with HIV.
      This is a Phase I, open-label trial in healthy women to investigate the pharmacokinetic
      interaction between the combination of ethinylestradiol and norethindrone and TMC278 25 mg
      once daily. The trial aims to allow further recommendations regarding the concurrent use of
      oral contraceptives and TMC278. The trial population will consist of 18 healthy women who are
      stable on oral contraceptives (OC), specifically ethinylestradiol and norethindrone, or who,
      if they are not currently using this OC, are willing to start or switch to this OC for the
      duration of the study.

      Healthy volunteers will receive the OC once daily for 21 days for at least 1 OC cycle prior
      to Day 1 [stabilizing OC cycle from Day -28 to Day -1]. During the second OC cycle [from Day
      1 to Day 28], subjects will receive the OC alone once daily for 21 days [Treatment A]. During
      the third OC cycle [from Day 29 to 56], subjects will receive the OC once daily for 21 days
      and in addition TMC278 25 mg q.d. in the morning for 15 days, starting on the first day of OC
      intake (Day 29) [Treatment B]. Full 24-hour pharmacokinetic profiles of ethinylestradiol and
      norethindrone will be determined after the first 2 weeks of the second OC cycle (Treatment A:
      OC alone; Day 15) and after the first 2 weeks of the third OC cycle (Treatment B: OC+TMC278;
      Day 43). A full 24-hour pharmacokinetic profile of TMC278 will be determined on Day 43. Blood
      samples on these days will be drawn just before drug intake (predose), and at 0.5, 1, 1.5, 2,
      3, 4, 5 (Day 43 only), 6, 9, 12, 16 (Day 43 only) and 24 hours postdose. Safety evaluations
      include evaluation of adverse events, physical examination including vital signs, ECGs and
      laboratory hematology and biochemistry assessments. Healthy volunteers will receive a tablet
      of ethinylestradiol and norethindrone OC once daily for 21 days for at least 1 OC cycle prior
      to Day 1. During the second OC cycle, healthy volunteers will receive a tablet of
      ethinylestradiol and norethindrone OC alone once daily for 21 days. During the third OC
      cycle, healthy volunteers will receive a tablet of ethinylestradiol and norethindrone once
      daily for 21 days and in addition a tablet of TMC278 25 mg once daily in the morning for 15
      days.
    

Intervention name(s): TMC278
Intervention type(s): Drug
Intervention MeSH terms: Rilpivirine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC278-TiDP6-C136; TMC278-C136; Healthy Volunteer