Clinical trial NCT01486004: A Study in Healthy Female Participants Investigating the Effect of TMC435 on the Pharmacokinetics of the Synthetic Hormones of the Oral Contraceptive Ovysmen
Official title: A Phase-I, Open-label Trial in Healthy Female Subjects to Investigate the Effect of TMC435 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C Virus
Keywords: Hepatitis C Virus
TMC435
TMC435-TiDP16-C124
TMC435-C124
HCV
Hepatitis C
Hep C
Healthy participants
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2011-12-06
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Participants must practicing a highly effective method of birth control before entry and agree to continue to use the same method throughout the study and for at least 30 days after last administration of study drug
* non-smoker for a least 3 months prior to screening

Exclusion Criteria:

* Women who are pregnant, breastfeeding, pre-menopausal or post-menopausal
* A positive Human Immunodeficiency Virus (HIV)-1 or HIV-2 test at screening
* A positive Hepatitis A, B and C test at screening
* A clinical significant abnormal finding in the gynaecological examination

Primary outcomes:
measure: Change in the steady-state plasma PK of ethinylestradiol following co-administration with TMC435
timeFrame: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
measure: Change in the steady-state plasma PK of norethindrone following co-administration with TMC435
timeFrame: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
Secondary outcomes:
measure: Change in the plasma levels of progesterone following co-administration of Ovysmen and TMC435.
timeFrame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
measure: Number of participants (%) with adverse events as a measure of safety and tolerability when combining TMC435 (150 mg, q.d.) with Ovysmen (35 µg ethinylestradiol + 1 mg norethindrone, q.d.)
timeFrame: Day of Screening + 21 days between screening and Day1 of first OC cycle + 28 days of first OC cycle + 28 days of second OC cycle
measure: Change in the plasma levels of luteinizing hormone following co-administration of Ovysmen and TMC435.
timeFrame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
measure: Change in the plasma levels of follicle-stimulating hormone following co-administration of Ovysmen and TMC435.
timeFrame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References: