A Study in Healthy Female Participants Investigating the Effect of TMC435 on the Pharmacokinetics of the Synthetic Hormones of the Oral Contraceptive Ovysmen
Information source: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis C Virus
Intervention: TMC435 (Drug); Ovysmen (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Tibotec Pharmaceuticals, Ireland Official(s) and/or principal investigator(s): Tibotec Pharmaceuticals, Ireland Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceuticals, Ireland
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.
Clinical Details
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 design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in the steady-state plasma PK of ethinylestradiol following co-administration with TMC435Change in the steady-state plasma PK of norethindrone following co-administration with TMC435
Secondary outcome: Change in the plasma levels of progesterone following co-administration of Ovysmen and TMC435.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.) Change in the plasma levels of luteinizing hormone following co-administration of Ovysmen and TMC435. Change in the plasma levels of follicle-stimulating hormone following co-administration of Ovysmen and TMC435.
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
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Female.
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
Locations and Contacts
Merksem, Belgium
Additional Information
Starting date: November 2011
Last updated: January 30, 2013
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