ContraceptionPhase 1NCT00779532
Thorough QT/QTc Study of Multiple Oral Doses of NOMAC-E2 (Org 10486 0 + Org 2317) in Healthy Women (Study 292011)(P05802)
A Phase 1 study testing Moxifloxacin and NOMAC-E2 (Org 10486-0 + Org 2317) in people with Contraception, run by Organon and Co.
Trial summary
The trial is a single-center randomized, double-blind, double-dummy, placebo and positive controlled, parallel group clinical trial. This trial investigated whether NOMAC-E2 (Org 10486 -0 + Org 2317), a new combined hormonal contraceptive, has potential to delay cardiac repolarization. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Moxifloxacin and NOMAC-E2 (Org 10486-0 + Org 2317)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 189 participants
- Where
- No sites listed yet
- Study dates
- May 2008to Nov 2008
- 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 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female (aged 18-50 years) with a body mass index (BMI) of 17 <= BMI <= 29 kg/m^2 at screening;
- Able and willing to use non-hormonal contraceptives during the trial from at least 2 weeks prior to Day 1 up to and including follow-up;
- Able and willing to sign the Informed Consent Form prior to screening evaluations;
- Subject is in a good age-appropriate healthy condition as established by medical history, physical examination, cardiac monitoring, electrocardiogram, results of biochemistry, hematology and urinalysis testing within 4 weeks prior to treatment as judged by the investigator;
- Normal 12-lead automatic ECG at screening and admission;
- Subject has a normal blood pressure at screening and admission;
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- Subject smokes less than 5 cigarettes or equivalent per day and is capable of not smoking from 48 hours prior drug administration on Day -1 and Day 14 until the last ECG has been taken on respectively Day 1 and Day 15;
- Able to refrain from all use of (methyl)xanthines (e.g. coffee, tea, cola, chocolate) from 48 hours prior to drug administration on Day -1 and Day 14 until the last ECG has been taken on respectively Day 1 and Day 15;
- Able to refrain from alcohol containing beverages from 24 hours prior to drug administration on Day -1 and Day 14 until the last ECG has been taken on respectively Day 1 and Day 15;
- Able to refrain from all use of grapefruit containing products from 14 days prior to first NOMAC-E2 dosing until the last ECG has been taken;
- Easy venous accessibility.
Who cannot join
- History of sensitivity/idiosyncrasy to the applied drugs or chemically related compounds or excipients which may be employed in the study or to any other unknown drug used in the past
- Use of any drug or substance within one week and hormonal contraception within 2 weeks prior to the first treatment day, except for paracetamol or topical medication without systemic exposure
- Present use or use during 2 months prior to the start of treatment of any drugs interfering with the trial medication;
- Clinically relevant history or presence of any medical disorder, potentially interfering with this trial (according to the investigator)
- Known or suspected pregnancy
- History of/or current abuse of drugs or alcohol or solvents, or positive drug or alcohol screen at screening and admission, as judged by the (sub-)investigator
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- Positive test result on hepatitis B surface antigen, hepatitis C antibody, or HIV 1/2 serology
- Participation in an investigational drug trial within 90 days prior to treatment
- Donation of blood within 90 days prior to treatment
- Contraindications for contraceptive steroids
- Breastfeeding or within 2 months after stopping breastfeeding prior to the start of trial medication.
- Present use or use within one month prior to treatment or within 10 half-lives in case the half-life > 3 days of any agent that is known to prolong the QT/QTc interval
- History of/or current risk factors for Torsade de Pointes (TdP) or life-threatening ventricular arrhythmia (e.g. heart failure, hypokaliemia, hypomagnesaemia, hypocalcaemia, family history of long or short QT syndrome, loss of consciousness)
About this study
Official title: A Randomized, Double-blind, Placebo and Positive Controlled, Parallel Group Trial to Investigate the Effect of Multiple Doses of NOMAC-E2 on QT/QTc Interval in Healthy Women
The trial is a single-center randomized, double-blind, double-dummy, placebo and positive controlled, parallel group clinical trial.
This trial investigated whether NOMAC-E2 (Org 10486 -0 + Org 2317), a new combined hormonal contraceptive, has potential to delay cardiac repolarization. The primary measure of cardiac repolarization in this trial is the Fridericia corrected QT interval (QTcF). QTcF represents the duration of ventricular depolarization and subsequent repolarization. A delay in cardiac repolarization creates an electrophysiological environment that favors the development of cardiac arrhythmias, most clearly torsade de pointes (TdP), but possibly other ventricular tachyarrhythmias.
Read more
The primary aim of this study is to investigate, if the administration of a therapeutic (2.5/1.5 mg) or supra-therapeutic (higher than required for treatment: 12.5/7.5 mg) dose of NOMAC-E2 administered over a period of 14 days will prolong the mean QTcF interval to values above the accepted threshold of regulatory concern.
In addition, a single dose of moxifloxacin will be administered in order to prove that sensitivity of the applied assay is sufficient to detect the prolongation of the QTcF-interval.
Secondary aims of this study are to evaluate the relation between concentrations of NOMAC (therapeutic and supra-therapeutic) after steady state has been reached in the subject's body, the time matched change in Estradiol E1 and E2 in relation to baseline and the QTcF intervals after multiple dose administration of NOMAC-E2.
Finally, the safety and tolerability of different treatments are investigated.
A total of 189 subjects will participate in this trial. The entire study duration is about 9 weeks with a 4-week screening period, 14-day treatment period and a follow-up period of about 3 weeks.
- Conditions
- Contraception
- Being tested
- Moxifloxacin, NOMAC-E2 (Org 10486-0 + Org 2317), Moxifloxacin placebo, NOMAC-E2 placebo
- Keywords
- Electrocardiography, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
Also called Avelox®
Capsules containing 400 mg moxifloxacin, on Day 14 only
NOMAC-E2 (Org 10486-0 + Org 2317)Drug
Tablets containing 2.5 mg NOMAC and 1.5 mg E2, once daily dosing, orally taken. Daily dose either NOMAC-E2 2.5/1.5 mg or 12.5/7.5 mg.
Moxifloxacin placeboDrug
Moxifloxacin-placebo capsule taken orally, Day -1 and Day 14 only
NOMAC-E2 placeboDrug
Tablets containing NOMAC-E2 placebo, once daily dosing, orally taken.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Once daily intake (orally) of 5 NOMAC-E2 placebo tablets from Day -1 to Day 14.
Once daily intake (orally) of one moxifloxacin placebo capsule at Day -1.
Once daily intake (orally) of one moxifloxacin capsule of 400 mg at Day 14. Receives: Drug: Moxifloxacin; Drug: Moxifloxacin placebo; Drug: NOMAC-E2 placebo |
| Group B | Experimental | Once daily intake (orally) of 4 NOMAC-E2 placebo tablets and 1 NOMAC-E2 (2.5/1.5 mg) tablet from Day 1 to Day 14.
Once daily intake (orally) of 5 NOMAC-E2 placebo tablets and 1 moxifloxacin placebo capsule at Day -1.
Once daily intake (orally) of 1 moxifloxacin placebo capsule at Day 14. Receives: Drug: NOMAC-E2 (Org 10486-0 + Org 2317); Drug: Moxifloxacin placebo; Drug: NOMAC-E2 placebo |
| Group C | Experimental | Once daily intake (orally) of 5 NOMAC-E2 (2.5/1.5 mg) tablets from Day 1 to Day 14.
Once daily intake (orally) of 5 NOMAC-E2 placebo tablets and 1 moxifloxacin placebo capsule at Day -1.
Once daily intake (orally) of 1 moxifloxacin placebo capsule at Day 14 Receives: Drug: NOMAC-E2 (Org 10486-0 + Org 2317); Drug: Moxifloxacin placebo; Drug: NOMAC-E2 placebo |
| Group D | Placebo comparator | Once daily intake (orally) of 5 NOMAC-E2 placebo tablets from Day -1 to Day 14.
Once daily intake (orally) of 1 moxifloxacin placebo capsule at Days -1 and 14. Receives: Drug: Moxifloxacin placebo; Drug: NOMAC-E2 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigate whether once daily multiple therapeutic and supra-therapeutic doses of NOMAC-E2 prolong the mean QTcF interval at steady state to the threshold of regulatory concern compared to placebo
Measured: 16 days
Establish assay sensitivity after single dose of 400 mg moxifloxacin
Measured: 16 days
Secondary outcomes (2)
evaluate the relation between steady state concentrations of NOMAC, time matched change from baseline in E1 and E2 and the QTcF intervals after multiple dosing of NOMAC-E2
Measured: 16 days
Investigate safety and tolerability of the various treatments
Measured: 64 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study startMay 2008
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 189 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779532
- Sponsor's protocol ID
- P05802
- Other IDs
- EudraCT # 2008-001649-25, 292011
- Status last verified
- Feb 2022
- First submitted
- 23 Oct 2008
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
de Kam PJ, van Kuijk J, Lillin O, Post T, Thomsen T. The effect of therapeutic and supratherapeutic oral doses of nomegestrol acetate (NOMAC)/17beta-estradiol (E2) on QTcF intervals in healthy women: results from a randomized, double-blind, placebo- and positive-controlled trial. Clin Drug Investig. 2014 Jun;34(6):413-20. doi: 10.1007/s40261-014-0190-5.
PubMed 24777591
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo and Positive Controlled, Parallel Group Trial to Investigate the Effect of Multiple Doses of NOMAC-E2 on QT/QTc Interval in Healthy Women
- ClinicalTrials.gov ID
- NCT00779532
- Acronym / sponsor ID
- P05802
- Conditions
- Contraception
- Keywords
- Electrocardiography, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 189 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 24 Oct 2008 (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 trial is a single-center randomized, double-blind, double-dummy, placebo and positive controlled, parallel group clinical trial.
This trial investigated whether NOMAC-E2 (Org 10486 -0 + Org 2317), a new combined hormonal contraceptive, has potential to delay cardiac repolarization. The primary measure of cardiac repolarization in this trial is the Fridericia corrected QT interval (QTcF). QTcF represents the duration of ventricular depolarization and subsequent repolarization. A delay in cardiac repolarization creates an electrophysiological environment that favors the development of cardiac arrhythmias, most clearly torsade de pointes (TdP), but possibly other ventricular tachyarrhythmias.
The primary aim of this study is to investigate, if the administration of a therapeutic (2.5/1.5 mg) or supra-therapeutic (higher than required for treatment: 12.5/7.5 mg) dose of NOMAC-E2 administered over a period of 14 days will prolong the mean QTcF interval to values above the accepted threshold of regulatory concern.
In addition, a single dose of moxifloxacin will be administered in order to prove that sensitivity of the applied assay is sufficient to detect the prolongation of the QTcF-interval.
Secondary aims of this study are to evaluate the relation between concentrations of NOMAC (therapeutic and supra-therapeutic) after steady state has been reached in the subject's body, the time matched change in Estradiol E1 and E2 in relation to baseline and the QTcF intervals after multiple dose administration of NOMAC-E2.
Finally, the safety and tolerability of different treatments are investigated.
A total of 189 subjects will participate in this trial. The entire study duration is about 9 weeks with a 4-week screening period, 14-day treatment period and a follow-up period of about 3 weeks.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: Moxifloxacin, Drug: Moxifloxacin placebo, Drug: NOMAC-E2 placeboOnce daily intake (orally) of 5 NOMAC-E2 placebo tablets from Day -1 to Day 14. Once daily intake (orally) of one moxifloxacin placebo capsule at Day -1. Once daily intake (orally) of one moxifloxacin capsule of 400 mg at Day 14. |
| Group B | Experimental | Drug: NOMAC-E2 (Org 10486-0 + Org 2317), Drug: Moxifloxacin placebo, Drug: NOMAC-E2 placeboOnce daily intake (orally) of 4 NOMAC-E2 placebo tablets and 1 NOMAC-E2 (2.5/1.5 mg) tablet from Day 1 to Day 14. Once daily intake (orally) of 5 NOMAC-E2 placebo tablets and 1 moxifloxacin placebo capsule at Day -1. Once daily intake (orally) of 1 moxifloxacin placebo capsule at Day 14. |
| Group C | Experimental | Drug: NOMAC-E2 (Org 10486-0 + Org 2317), Drug: Moxifloxacin placebo, Drug: NOMAC-E2 placeboOnce daily intake (orally) of 5 NOMAC-E2 (2.5/1.5 mg) tablets from Day 1 to Day 14. Once daily intake (orally) of 5 NOMAC-E2 placebo tablets and 1 moxifloxacin placebo capsule at Day -1. Once daily intake (orally) of 1 moxifloxacin placebo capsule at Day 14 |
| Group D | Placebo comparator | Drug: Moxifloxacin placebo, Drug: NOMAC-E2 placeboOnce daily intake (orally) of 5 NOMAC-E2 placebo tablets from Day -1 to Day 14. Once daily intake (orally) of 1 moxifloxacin placebo capsule at Days -1 and 14. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Female (aged 18-50 years) with a body mass index (BMI) of 17 <= BMI <= 29 kg/m^2 at screening;
- Able and willing to use non-hormonal contraceptives during the trial from at least 2 weeks prior to Day 1 up to and including follow-up;
- Able and willing to sign the Informed Consent Form prior to screening evaluations;
- Subject is in a good age-appropriate healthy condition as established by medical history, physical examination, cardiac monitoring, electrocardiogram, results of biochemistry, hematology and urinalysis testing within 4 weeks prior to treatment as judged by the investigator;
- Normal 12-lead automatic ECG at screening and admission;
Key exclusion criteria (13 listed)
- History of sensitivity/idiosyncrasy to the applied drugs or chemically related compounds or excipients which may be employed in the study or to any other unknown drug used in the past
- Use of any drug or substance within one week and hormonal contraception within 2 weeks prior to the first treatment day, except for paracetamol or topical medication without systemic exposure
- Present use or use during 2 months prior to the start of treatment of any drugs interfering with the trial medication;
- Clinically relevant history or presence of any medical disorder, potentially interfering with this trial (according to the investigator)
- Known or suspected pregnancy
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 |
|---|---|---|
| MoxifloxacinAlso: Avelox®Capsules containing 400 mg moxifloxacin, on Day 14 only | Drug | Group A |
| NOMAC-E2 (Org 10486-0 + Org 2317)Tablets containing 2.5 mg NOMAC and 1.5 mg E2, once daily dosing, orally taken. Daily dose either NOMAC-E2 2.5/1.5 mg or 12.5/7.5 mg. | Drug | Group B, Group C |
| Moxifloxacin placeboMoxifloxacin-placebo capsule taken orally, Day -1 and Day 14 only | Drug | Group A, Group B, Group C, Group D |
| NOMAC-E2 placeboTablets containing NOMAC-E2 placebo, once daily dosing, orally taken. | Drug | Group A, Group B, Group C, Group D |
Primary outcome
Investigate whether once daily multiple therapeutic and supra-therapeutic doses of NOMAC-E2 prolong the mean QTcF interval at steady state to the threshold of regulatory concern compared to placebo
Time frame: 16 days
Establish assay sensitivity after single dose of 400 mg moxifloxacin
Time frame: 16 days
2 secondary outcomes
evaluate the relation between steady state concentrations of NOMAC, time matched change from baseline in E1 and E2 and the QTcF intervals after multiple dosing of NOMAC-E2
Time frame: 16 days
Investigate safety and tolerability of the various treatments
Time frame: 64 days
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 16 Feb 2022.
- Derived from this study: PubMed 24777591de Kam PJ, van Kuijk J, Lillin O, Post T, Thomsen T. The effect of therapeutic and supratherapeutic oral doses of nomegestrol acetate (NOMAC)/17beta-estradiol (E2) on QTcF intervals in healthy women: results from a randomized, double-blind, placebo- and positive-controlled trial. Clin Drug Investig. 2014 Jun;34(6):413-20. doi: 10.1007/s40261-014-0190-5.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Moxifloxacin and NOMAC-E2 (Org 10486-0 + Org 2317) in people with Contraception, run by Organon and Co.
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 11 inclusion and 13 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 16 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Investigate whether once daily multiple therapeutic and supra-therapeutic doses of NOMAC-E2 prolong the mean QTcF interval at steady state to the threshold of regulatory concern compared to placebo (time frame: 16 days). 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?
On the ClinicalTrials.gov record for NCT00779532, which also lists 1 linked publication.
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 16 Feb 2022.