Prevention of Pregnancy Clinical Trial
Official title:
A Single-center, Randomized, Open-label, Two-arm Study to Evaluate the Ovarian Function Inhibition of a Monophasic Combined Oral Contraceptive (COC) Containing 15 mg Estetrol (E4) and 3 mg Drospirenone (DRSP) and a Monophasic COC Containing 20mcg Ethinylestradiol (EE)/3 mg DRSP (YAZ®), Administered Orally Once Daily in a 24/4 Day Regimen for Three Consecutive Cycles
| Verified date | April 2023 |
| Source | Estetra |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 82 |
| Est. completion date | June 8, 2018 |
| Est. primary completion date | June 8, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Female |
| Age group | 18 Years to 35 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Dinox BV | Groningen |
| Lead Sponsor | Collaborator |
|---|---|
| Estetra |
Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Proportion of subjects with ovarian inhibition at treatment Cycle 1 | 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. |
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). | |
| Primary | Proportion of subjects with ovarian inhibition at treatment Cycle 3 | 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. |
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). | |
| Secondary | Serum level of luteinizing hormone (LH) | Blood samples will be taken at regular time points defined in the time frame. | 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) | |
| Secondary | Serum level of follicle stimulating hormone (FSH) | Blood samples will be taken at regular time points defined in the time frame. | 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) | |
| Secondary | Serum level of estradiol (E2) | Blood samples will be taken at regular time points defined in the time frame. | 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) | |
| Secondary | Serum level of progesterone (P) | Blood samples will be taken at regular time points defined in the time frame. | 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) | |
| Secondary | Maximum endometrial thickness | Endometrial thickness will be measured using transvaginal ultrasound (TVUS). Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle. | 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) | |
| Secondary | Mean diameter of the largest follicle | Follicular size will be measured using TVUS. | Day 3 to Day 24 of Post-Treatment Cycle | |
| Secondary | Number of participants who experience at least one Treatment-Emergent Adverse Event (TEAE) | Day 1 to Follow-Up Visit (+ 30 days) | ||
| Secondary | Number of participants who experience pregnancy during treatment | Cycle 1 Day 1 to Follow-Up Visit (+ 30 days) (each treatment cycle = 28 days) | ||
| Secondary | Number of participants who experience a clinically significant change in physical examination results | Day 1 to End of Follow-Up Visit (+ 30 Days) | ||
| Secondary | Number of participants who experience a clinically significant change in gynecological examination results | Day 1 to End of Follow-Up Visit (+ 30 Days) | ||
| Secondary | Number of participants who experience a clinically significant change in clinical laboratory results | Day 1 to End of Follow-Up Visit (+ 30 Days) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) |
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