E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore the pharmacodynamic (PD) effects, and specifically on occurrence and timing of ovulation with pregnancy risk, of ellaOne taken after pills of combined oral contraception (COC) were missed for three consecutive days during the first week of COC use and were resumed either on the day of ellaOne intake or five days later. |
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E.2.2 | Secondary objectives of the trial |
To explore in the 5 days after ellaOne intake the PD effects on ovarian activity (particularly ovulation risk) of ellaOne taken after 3 consecutive COC pills missed in 1st week of use then resumed on ellaOne intake day or 5 days later
To show ovarian activity (particularly occurrence and timing of ovulations) in baseline period (BAS); assess similarity level with experimental period (EXP) where women missed 3 COC pills, took ellaOne, resumed COC on ellaOne intake day or 5 days later
To evaluate ovarian quiescence (OQ) duration &proportion of women with OQ over the 28-day BAS
To evaluate OQ duration and proportion of women with OQ over the 28-day EXP where women missed 3 COC pills, took ellaOne, resumed COC on ellaOne intake day or 5 days later; with specific attention to 5 days after ellaOne intake
To evaluate safety (specifically effects on spotting and vaginal bleeding) of ellaOne taken after 3 COC pills missed in 1st week of use then resumed on ellaOne intake day or 5 days later |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Women aged 18-30 years old at screening
•Women relying on a COC (containing 30 μg ethinyl estradiol and 7-day pill-free (or placebo) interval) as their primary method of contraception for at least 2 cycles before they enter the baseline period and willing to continue with a COC for at least one cycle after end of experimental period
•Not at risk of pregnancy:
onot sexually active, or
owilling to protect all acts of intercourse with condoms, or
ohaving undergone surgical sterilization (tubal ligation), or
opartner sterilized or vasectomized
•BMI < 30.0 kg/m2
•Women able to give informed consent form to participate in the study and willing to comply with all study constraints
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E.4 | Principal exclusion criteria |
• Currently pregnant as confirmed by positive high-sensitivity urine pregnancy test
• Currently breast-feeding
• Current use of an IUD
• Use of any hormonal contraception other than the study medications during the study
• Liver enzymes levels at the screening visit above three times the upper limit of normal or any other anomalies in safety labs recognized as clinically significant by the investigator
• Known hypersensitivity to the ingredients of the test active substances or excipients
• Any contraindications to Levora® (per SPC)
• Pap smear score ≥ 3 in the past 11 months
• Known Polycystic Ovary Syndrome (PCOS)
• Clinically significant abnormalities observed on TVU performed at screening visit
• Cancer (past history of any carcinoma or sarcoma)
• Known abnormal thyroid status not adequately stabilized or substituted by current treatment
• Chronic treatment with oral glucocorticoids
•Hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Known or suspected alcoholism or drug abuse
• Concomitant use of medication thought to interact with ellaOne® or Levora® (per SPCs)
• Current participation in any other trial of an investigational medicine or participation in the past three months before start of baseline period
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E.5 End points |
E.5.1 | Primary end point(s) |
a. Ovarian Activity Score (quiescence, ovarian activity, ovulation at risk of pregnancy)
b.Occurrence of ovulation with risk of pregnancy
c.Time to ovulation with risk of pregnancy
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Follicular diameter and levels of hormones in serum will be measured throughout baseline, experimental and post-experimental periods
Ovulation at risk of pregnancy will be defined as:
a. A postovulatory image is observed on transvaginal ultrasound. It is defined as follow:
Image observed after abrupt disappearance of FLS OR
Image observed after reduction in size of the leading follicle > 4 mm* at two consecutive visits OR
Haemorrhagic and cystic corpus luteum (FLS at least as large as the leading follicle before ovulation)
b.Estradiol level >0.1 nmol/L
c.Progesterone level >10 nmol/L at two consecutive visits or one level >30 nmol/L
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E.5.2 | Secondary end point(s) |
Safety of treatment intake |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Analysis of spotting / vaginal bleeding under treatment and occurrence of adverse events. Vital signs and laboratory safety parameters will also be described by quantitative statistics, at each time point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |