A Study in Healthy Female Participants Investigating the Effect of TMC435 on the Pharmacokinetics of the Synthetic Hormones of the Oral Contraceptive Ovysmen

NCT ID: NCT01486004

Last Updated: 2013-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-01-31

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.

Conditions

Hepatitis C Virus

Keywords

Hepatitis C Virus; TMC435; TMC435-TiDP16-C124; TMC435-C124; HCV; Hepatitis C; Hep C; Healthy participants

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

001

35 µg ethinylestradiol and 1 mg norethindrone once daily for first 21 days in each OC cycle (2 OC cycles in total) + 150 mg capsule once daily for 10 days (Day12 till and including Day21) in 2nd OC cycle

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

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.

Ovysmen

Intervention Type: DRUG

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)

Interventions

TMC435

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.

Intervention Type: DRUG

Ovysmen

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 Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals, Ireland Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceuticals, Ireland

Locations

Merksem, , Belgium

Countries

Belgium

Other Identifiers

TMC435-TiDP16-C124

Identifier Type: OTHER

Identifier Source: secondary_id

2011-003022-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100683

Identifier Type: -

Identifier Source: org_study_id