Prevention of Pregnancy
Conditions
Brief summary
A combined oral contraceptive (COC) containing 15 mg E4 and 3 mg DRSP administered for 24 days followed by 4 placebo tablets, is being evaluated for further development. This study will investigate the effect of this COC on ovarian function inhibition, levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone during 3 treatment cycles in comparison with the reference COC 20 mcg EE/3 mg DRSP.
Interventions
15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
Sponsors
Estetra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy female subjects, as determined by medical history, physical examination including breast examination, gynecological examination (including cervical smear \[Pap smear\]), vital signs, ECG, echocardiogram, and laboratory tests. * Negative pregnancy test at subject screening. * Women who ovulate in the Pre-Treatment Cycle. * Willing to use a non-hormonal method of contraception (e.g. condom) during the wash-out period, Pre-Treatment Cycle and Post-Treatment Cycle. * BMI between 18.0 and 35.0 kg/m², inclusive, at time of Screening. * Able to fulfill the requirements of the protocol and have indicated a willingness to participate in the study by providing written informed consent form (ICF).
Exclusion criteria
* Irregular menstrual cycle. * Amenorrhea or abnormal uterine bleeding. * Clinically relevant abnormal laboratory result at Screening. * Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound. * Known hypersensitivity to any of the investigational or reference product ingredients. * Intention to become pregnant during the course of the study. * Pregnancy during accurate hormonal contraceptive use in the past. * Dyslipoproteinemia requiring active treatment with antilipidemic agent. * Diabetes mellitus with vascular involvement (nephropathy, retinopathy, neuropathy, other) or diabetes mellitus of more than 20-year duration. * Any arterial hypertension. * Any condition associated with an increased risk of venous thromboembolism and/or arterial thromboembolism. * Complicated valvular heart disease. * History of pregnancy-related cardiomyopathy or moderately or severely impaired cardiac function. * Systemic lupus erythematosus. * Presence or history of migraine with aura. * Abnormal Papanicolaou (PAP) smear result. * Presence of an undiagnosed breast mass. * Current symptomatic gallbladder disease. * History of COC-related cholestasis. * Presence or history of severe hepatic disease. * Presence or history of pancreatitis if associated with hypertriglyceridemia. * Porphyria. * Presence or history of hepatocellular adenoma or malignant liver tumors. * Renal impairment. * Hyperkaliemia or presence of conditions that predispose to hyperkaliemia. * Presence or history of hormone-related malignancy. * History of non-hormone-related malignancy within 5 years before Screening. Subjects with a non-melanoma skin cancer are allowed in the study. * Use of drugs potentially triggering interactions with COCs. * History of alcohol or drug abuse. * Any prior procedure, disease or condition that could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the investigational product. * Uncontrolled thyroid disorders. * Have received an investigational drug within the last 2 cycles prior to start of Pre-Treatment Cycle. Subjects who participated in an oral contraceptive clinical study, using Food and Drug Administration (FDA)/European Union (EU) approved active ingredients, may start the Pre-Treatment Cycle one cycle after last medication intake of the preceding study. * Sponsor, contract research organization (CRO) or PI's site personnel directly affiliated with this study. * Is judged by the PI to be unsuitable for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with ovarian inhibition at treatment Cycle 1 | All assessments will be performed once every 3 days starting treatment Cycle 1 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days). | Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on: * the follicular size assessed by transvaginal ultrasound (TVUS) * endogenous hormone levels: serum E2, and serum progesterone. |
| Proportion of subjects with ovarian inhibition at treatment Cycle 3 | All assessments will be performed once every 3 days starting treatment Cycle 3 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days). | Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on: * the follicular size assessed by TVUS * endogenous hormone levels: serum E2, and serum progesterone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum level of estradiol (E2) | On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days) | Blood samples will be taken at regular time points defined in the time frame. |
| Serum level of progesterone (P) | On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days) | Blood samples will be taken at regular time points defined in the time frame. |
| Maximum endometrial thickness | From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days) | Endometrial thickness will be measured using transvaginal ultrasound (TVUS). Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle. |
| Mean diameter of the largest follicle | Day 3 to Day 24 of Post-Treatment Cycle | Follicular size will be measured using TVUS. |
| Number of participants who experience at least one Treatment-Emergent Adverse Event (TEAE) | Day 1 to Follow-Up Visit (+ 30 days) | — |
| Number of participants who experience pregnancy during treatment | Cycle 1 Day 1 to Follow-Up Visit (+ 30 days) (each treatment cycle = 28 days) | — |
| Number of participants who experience a clinically significant change in physical examination results | Day 1 to End of Follow-Up Visit (+ 30 Days) | — |
| Serum level of luteinizing hormone (LH) | On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days) | Blood samples will be taken at regular time points defined in the time frame. |
| Number of participants who experience a clinically significant change in clinical laboratory results | Day 1 to End of Follow-Up Visit (+ 30 Days) | — |
| Number of participants who experience a clinically significant change in electrocardiogram (ECG) results | Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days) | — |
| Number of participants who experience a clinically significant change in echocardiogram results | Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days) | — |
| Change from Baseline in diastolic blood pressure | From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days) | — |
| Change from Baseline in systolic blood pressure | From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days) | — |
| Change from Baseline in pulse rate | From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days) | — |
| Number of participants who experience a clinically significant change in gynecological examination results | Day 1 to End of Follow-Up Visit (+ 30 Days) | — |
| Serum level of follicle stimulating hormone (FSH) | On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days) | Blood samples will be taken at regular time points defined in the time frame. |
Countries
Netherlands
Outcome results
None listed