Hepatitis C VirusPhase 1NCT01486004
A Study in Healthy Female Participants Investigating the Effect of TMC435 on the Pharmacokinetics of the Synthetic Hormones of the Oral Contraceptive Ovysmen
A Phase 1 study testing TMC435 and Ovysmen in people with Hepatitis C Virus, run by Tibotec Pharmaceuticals, Ireland at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C Virus
- What is being tested?
- TMC435 and Ovysmen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2011to Jan 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- TMC435, Ovysmen
- Keywords
- Hepatitis C Virus, TMC435, TMC435-TiDP16-C124, TMC435-C124, HCV, Hepatitis C, Hep C, Healthy participants
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435Drug
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.
OvysmenDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 001 | Experimental | 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 Receives: Drug: TMC435; Drug: Ovysmen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the steady-state plasma PK of ethinylestradiol following co-administration with TMC435
PK characteristics of ethinylestradiol and norethindrone are determined based on their respective plasma levels at one time point (Day19, 20 and 22) and at 10 time points (Day22). Standard PK parameters such as C0h, Cmin, Cmax, Tmax, AUC24h etc. will be determined.
Measured: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
Change in the steady-state plasma PK of norethindrone following co-administration with TMC435
PK characteristics of ethinylestradiol and norethindrone are determined based on their respective plasma levels at one time point (Day19, 20 and 22) and at 10 time points (Day22). Standard PK parameters such as C0h, Cmin, Cmax, Tmax, AUC24h etc. will be determined.
Measured: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
Secondary outcomes (4)
Change in the plasma levels of progesterone following co-administration of Ovysmen and TMC435.
Plasma levels of progesterone.
Measured: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
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.)
Measured: 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
Change in the plasma levels of luteinizing hormone following co-administration of Ovysmen and TMC435.
Plasma levels of luteinizing hormone.
Measured: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
Change in the plasma levels of follicle-stimulating hormone following co-administration of Ovysmen and TMC435.
Plasma levels of follicle-stimulating hormone.
Measured: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2011 (estimated)
- Study startNov 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01486004
- Sponsor's protocol ID
- CR100683
- Other IDs
- TMC435-TiDP16-C124, 2011-003022-26
- Status last verified
- Jan 2013
- First submitted
- 21 Oct 2011
- Last updated
- 31 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01486004
- Acronym / sponsor ID
- CR100683
- Conditions
- Hepatitis C Virus
- Keywords
- Hepatitis C Virus, TMC435, TMC435-TiDP16-C124, TMC435-C124, HCV, Hepatitis C, Hep C, Healthy participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 6 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 001 | Experimental | Drug: TMC435, Drug: Ovysmen35 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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC435Type = 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. | Drug | 001 |
| OvysmenType = 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) | Drug | 001 |
Primary outcome
Change in the steady-state plasma PK of ethinylestradiol following co-administration with TMC435
Time frame: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
PK characteristics of ethinylestradiol and norethindrone are determined based on their respective plasma levels at one time point (Day19, 20 and 22) and at 10 time points (Day22). Standard PK parameters such as C0h, Cmin, Cmax, Tmax, AUC24h etc. will be determined.
Change in the steady-state plasma PK of norethindrone following co-administration with TMC435
Time frame: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.
PK characteristics of ethinylestradiol and norethindrone are determined based on their respective plasma levels at one time point (Day19, 20 and 22) and at 10 time points (Day22). Standard PK parameters such as C0h, Cmin, Cmax, Tmax, AUC24h etc. will be determined.
4 secondary outcomes
Change in the plasma levels of progesterone following co-administration of Ovysmen and TMC435.
Time frame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
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.)
Time frame: 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
Change in the plasma levels of luteinizing hormone following co-administration of Ovysmen and TMC435.
Time frame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
Change in the plasma levels of follicle-stimulating hormone following co-administration of Ovysmen and TMC435.
Time frame: Measured on Day1, 19, 20 and 21 of 2nd OC cycle. Reference is Day1, 19, 20 and 21 of 1st OC cycle.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMC435 and Ovysmen in people with Hepatitis C Virus, run by Tibotec Pharmaceuticals, Ireland at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the steady-state plasma PK of ethinylestradiol following co-administration with TMC435 (time frame: Measured on Day19 till and including Day22 of 2nd OC cycle. Reference is Day19 till and including Day22 of 1st OC cycle.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2013.