A Study in Healthy Female Participants Investigating the Effect of TMC435 on the Pharmacokinetics of the Synthetic Hormones of the Oral Contraceptive Ovysmen
Condition: Hepatitis C Virus
MeSH terms: Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the effect of steady-state concentrations of
      TMC435 (administered once a day) on the steady-state pharmacokinetics of ethinylestradiol and
      norethindrone (administered once a day) and on the levels of progesterone, luteinizing
      hormone and follicle-stimulating hormone, in healthy female participants. Ethinlyestradiol
      and norethindrone are synthetic hormones, which constitute the oral contraceptive Ovysmen.
      Also the short-term safety and tolerability of the co-administration of TMC435 and Ovysmen
      will be studied. Steady-state is a term that means that the drug has been given long enough
      so that the plasma concentrations will remain the same with each subsequent dose. TMC435 is
      being investigated for the treatment of chronic hepatitis C virus (HCV) infection.
      Pharmacokinetics (PK) means how the drug is absorbed into the bloodstream, distributed in the
      body and eliminated from the body. A contraceptive is a method that prevents pregnancy.
    

Detailed description: 
      This is a Phase I, open-label (both participant and investigator know the name of the
      medication given at a certain moment) trial in 18 healthy female participants to investigate
      the effect of TMC435 at steady-state on the steady-state pharmacokinetics of ethinlyestradiol
      and norethindrone. Ethinylestradiol (35 µg) and norethindrone (1.0 mg) are the components of
      Ovysmen, which is a widely used oral contraceptive (OC). All subjects will receive OC therapy
      for 2 complete OC cycles. During the first cycle, participants will receive Ovysmen alone,
      once daily, for the first 21 days. An OC- free period is respected from Day22 till and
      including Day28. During the second OC cycle, participants will receive again Ovysmen once
      daily during the first 21 days plus TMC435 150 mg once daily as of Day12 till and including
      Day21. Next, a OC-free period from Day22 till and including Day28 is established. Full
      24-hour PK profiles of ethinylestradiol and norethindrone will be determined at the last day
      of OC treatment of the first OC cycle (i.e. on Day21) and on the last day of OC treatment of
      the second OC cycle (i.e. Day21). Full 24-hour PK profile of TMC435 will be determined on
      Day21 of second OC cycle. Pharmacodynamic (how the body reacts on the drug) assessments of
      serum levels of progesterone, luteinizing hormone and follicle-stimulating hormone (these
      hormones are involved in ovulation and in preparation of the womb for a pregnancy) will be
      done on Day1, 19, 20 and 21 of both OC cycles. Safety and tolerability will be assessed
      during the study period and during follow up. Blood and urine safety samples,
      electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at
      screening, Day1, Day21 and Day22 of each OC cycle, and at the follow-up visit about 5 to 7
      days after last TMC435 intake. A physical examination will be performed at screening, Day1
      and Day20 of each OC cycle, and at the follow-up visit about 5 to 7 days after last TMC435
      intake. Participants are admitted to the unit on Day20 in the morning and are discharged on
      Day22, for both OC cycles.
    

Intervention name(s): TMC435; Ovysmen
Intervention type(s): Drug; Drug
Intervention description(s): Type = exact number, unit = mg, number = 150, form = capsule, route = oral use. Capsule is taken once daily for 10 days (Day12 till and including Day21) in 2nd OC cycle.; Type = exact number, unit = mg, number = 35µg/1mg, form = tablet, route = oral use. 35 µg ethinylestradiol and 1 mg norethindrone once daily for first 21 days in each OC cycle (2 OC cycles in total)
Intervention MeSH terms: Simeprevir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatitis C Virus; TMC435; TMC435-TiDP16-C124; TMC435-C124; HCV; Hepatitis C; Hep C; Healthy participants