BioequivalencePhase 1NCT03749733
Bioequivalence of Two Fixed-dose Combination Tablets Containing Estradiol and Nomegestrol Acetate
A Phase 1 study testing Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product) and Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product) in people with Bioequivalence, run by Grünenthal GmbH at 1 site in Mexico.
Trial summary
This study will investigate the bioavailability in fasting post-menopausal women of 2 film-coated tablet formulations containing 1.5 milligrams (mg) of estradiol and 2.5 mg of nomegestrol acetate. The study will be performed at a single site. Read more about this study
- Who is it for?
- Ages 40 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Bioequivalence
- What is being tested?
- Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product) and Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteMexico
- Study dates
- Oct 2019to Dec 2019
- 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 40 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participation will be voluntary and according to the guidelines proposed by the Health General Law (Mexico), and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the current Brazilian laws, and Good Clinical Practice.
- Only post-menopausal women aged between 40 years and 65 years who meet any of the following criteria:
- 12 months of spontaneous amenorrhea.
- 6 months of spontaneous amenorrhea with follicle-stimulating hormone levels above 40 international units per liter and below 20 nanograms per liter estradiol.
- Bilateral oophorectomy with or without hysterectomy.
- The body mass index must be between 18.5 and 29.99 kilograms per square meter according to the Quetelet index.
Show all 30Show fewer
- Participants must be healthy determined by the results of a complete clinical history recorded by the clinical investigational site physicians and the results of the laboratory examinations done by a certified clinical laboratory.
- Participants with pre-existing illnesses must be controlled with stable doses of medication for a period of at least 3 months.
- Non-smoker and/or not having used nicotine or nicotine-containing products (e.g., nicotine plasters) within 3 months prior to the beginning of the study.
- The allowed limits of variation within normal in the screening visit will be: systolic blood pressure (sitting) below 120 mmHg, diastolic blood pressure below 80 mmHg, heart rate between 50 and 100 beats per minute and respiratory rate between 14 and 20 breaths per minute according to the current standard operating procedure. Vital signs will be measured after 10 minutes of resting in a sitting position.
- Laboratory and other examinations to be conducted for the inclusion of participants will be:
- Complete blood count: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte distribution width, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
- Blood chemistry 27 elements: glucose, urea, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, uric acid, cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL), cholesterol, non-HDL cholesterol, atherogenic index, total protein, albumin, globulins, albumin/globulin ratio, total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, total alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, iron, calcium, sodium, potassium, and chloride.
- Urinalysis: Physical examination (color, appearance, density); chemical examination (pH, leukocytes, nitrite, protein, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysmorphic erythrocytes, casts, crystals, squamous epithelial cells, tubular renal cells, mucus, bacteria and yeasts).
- Hepatitis B screening (Antibody to hepatitis B core antigen [Anti-HBc], antibody to hepatitis B surface antigen [HBs-Ab], antibody to hepatitis B surface antigen [Anti-HBs]) and hepatitis C antibodies.
- HIV test: Antibodies to the human immunodeficiency virus (Anti-HIV 1 and 2).
- Venereal disease research laboratory test (VDRL).
- Urine drugs of abuse test at the screening visit and on Day 0 (approximately 12 hours prior to the administration of the investigational medicinal product [IMP] on the previous day) on both study periods.
- Alcohol breath test on Day 0 (prior to the administration of the investigational medicinal product on the previous day) on both study periods.
- 12-lead electrocardiogram which will be performed after resting for 10 minutes in a sitting position.
- In addition, each participant will undergo the following examinations:
- Complete gynecological profile:
- Follicle-stimulating hormone (FSH).
- Luteinizing hormone (LH).
- Serum estradiol.
- Serum progesterone.
- Serum prolactin.
- Bilateral mammography (with Breast Imaging Reporting and Data System [BI-RADS] 1 or 2 results).
- Transvaginal ultrasound (without clinically significant findings).
- Pap smear (without clinically significant findings).
Who cannot join
- Participants with a history of the following diseases: cardiovascular (myocardial infarction, not-controlled hypertension, thromboembolic arterial or venous diseases), renal (kidney failure), hepatic (hepatitis, jaundice), muscular, metabolic, gastrointestinal, neurologic (cerebrovascular disease), psychiatric (depression) endocrinological (not-controlled diabetes mellitus), hematopoietic, respiratory or other organic abnormalities that are not appropriately controlled and that require a pharmacological treatment that could result in a drug interaction with the study medication. Women who have had muscular trauma within 21 days previous to the study will also be excluded.
- History of major surgeries (cranial surgery, thorax, abdomen or extensive surgeries in extremity requiring the use of general or regional anesthesia and/or respiratory support) within 3 months previous to the study.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer.
- History of lactose intolerance.
- Participants who have been exposed to medications known to be hepatic enzyme inducers or inhibitors within 72 hours previous to the start of the study.
- Participants who have taken any type of vitamin supplements (with or without prescription) or herbal remedies within 30 days (or 7 half-lives) previous to the start of the study.
Show all 30Show fewer
- Participants undergoing hormone replacement therapy or taking thyroid hormones.
- Participants with uterine bleeding.
- Participants with endometrial thickness equal to or greater than 7 mm as determined in the transvaginal ultrasound.
- Participants who have been hospitalized for any reason within 6 months prior to study start.
- Participants who have taken investigational medicinal products from other investigations within 180 days (i.e., 6 months) prior to study start.
- Participants with a history of allergy or hypersensitivity to the study medication (estradiol/nomegestrol), any other medication, food, or substance.
- Participants who have consumed alcohol, carbonated beverages, or beverages that contain methylxanthines (coffee, tea, cocoa, chocolate, mate, cola, etc.), grapefruit juice, or charbroiled foods within 12 hours prior to the start of the hospitalization period.
- Participants with any of the following results for hepatitis B: acute infection, chronic infection, or unclear result based on the interpretation of results of the hepatitis B virus serology (CDC Interpretation of Hepatitis B Serologic Test Results).
- Participants who have donated or lost more than 450 milliliters of blood within 90 days prior to study start.
- Participants with a history of dependence/abuse of alcohol or psychoactive substances.
- Participants requiring a special diet for any reason e.g., vegetarian.
- Participants unable to understand the nature, objectives, and possible consequences of the study.
- Evidence of the participant's uncooperativeness during the conduct of the study (unable follow the instructions and requirements of the study personnel).
- Positive results for drugs of abuse or alcohol breath tests.
- Participants who are not registered in the Comisión Federal para la Protección contra Riesgos Sanitarios [COFEPRIS]) webpage.
- Relationship of subordination between the participants and the investigators.
- Sponsor or clinical site employees.
- Discontinuation criteria:
- Safety and well-being of the participant.
- Lack of adherence to the procedures and therefore non-compliance with the protocol.
- Medical reasons (serious adverse events), adverse reactions to the study medication classified as severe.
- Uncooperative attitude during the conduct of the study (unable follow the instructions and requirements of the study personnel).
- Recurring or intercurrent disease (not controlled).
- Withdrawal of consent to participate in the study.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Investigacíon Farmacológica y Biofarmacéutica (IFaB), S.A.P.I. de C.V.
Mexico City, C.P. 14610
About this study
Official title: Single Site, Open-label, Randomized, Two Treatments, Two Periods, Two Sequences, Crossover Single-dose Trial to Investigate the Bioequivalence of Two Oral Formulations of a Fixed-dose Combination Tablet Containing 1.5 mg Estradiol and 2.5 mg Nomegestrol Acetate (Product of Laboratorios Andrómaco S.A. [Test Product] Versus Stezza, Product of Merck Sharp & Dohme Farmacêutica Ltda. [Reference Product]) in Postmenopausal Women Under Fasting Conditions
This study will investigate the bioavailability in fasting post-menopausal women of 2 film-coated tablet formulations containing 1.5 milligrams (mg) of estradiol and 2.5 mg of nomegestrol acetate.
The study will be performed at a single site. Participants will take a single oral dose of the test product and reference product in 2 periods and 2 sequences (either test after reference or reference after test). There will be a washout of at least 21 days between each study period.
Read the detailed description
The primary objective of the study is to investigate the relative bioavailability of estradiol and nomegestrol of 2 film-coated tablet formulations with estradiol 1.5 mg and nomegestrol acetate 2.5 mg and to demonstrate bioequivalence of both formulations in terms of rate and extent of absorption:
- Test Product: new product manufactured by Laboratorios Andrómaco S.A.
- Reference Product: Stezza [Trademark], product of Merck Sharp \& Dohme Farmacêutica Ltda.
The 90% confidence intervals for the intra-subject coefficient of variation (Test versus Reference Product) for the main pharmacokinetic parameters area under the plasma concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72 hours (AUC0-72), and maximum plasma concentration (Cmax) for total estradiol/estrone and nomegestrol will be determined.
Participants will be confined in the study site for approximately 36 hours during each study period (for 12 hours pre-dosing and for 24 hours post dosing) during which pharmacokinetic (PK) blood samples will be obtained. Three blood samples will be taken before the film-coated tablet is administered (at pre-dose: -1.0, -0.5, and 0 h) and 16 samples up to 24 hours after the administration in each period. Participants will return to the site to provide additional blood samples at 36 h, 48 h, and 72 h post-dose.
The washout period between the two study periods will be at least 21 days.
The samples from each participant will be analyzed with 2 methods of high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays to quantify total estradiol/estrone and nomegestrol in plasma with citrate phosphate dextrose anticoagulant. The blood samples taken at pre-dose will be taken to establish the baseline concentrations of total estrone and estradiol. The baseline-corrected and uncorrected AUCs and Cmax will be calculated.
The safety objective is to evaluate the tolerability of both formulations in post-menopausal women by collecting adverse events.
- Conditions
- Bioequivalence
- Being tested
- Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product), Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product)
- Keywords
- Bioequivalence, Estradiol, Nomegestrol acetate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product)Drug
Also called Stezza (Trade Mark)
Marketed Drug
Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product)Drug
Investigational Medicinal Product
| Study group | Role | What they receive |
|---|---|---|
| Test Product | Experimental | Participants will receive a single film-coated tablet of the test formulation containing estradiol 1.5 mg/nomegestrol acetate 2.5 mg.
The tablet will be taken with water and in a fasting condition. Receives: Drug: Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product) |
| Reference Product | Active comparator | Participants will receive a single film-coated tablet of the marketed reference formulation containing estradiol 1.5 mg/nomegestrol acetate 2.5 mg.
The tablet will be taken with water and in a fasting condition. Receives: Drug: Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total estrone (corrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estrone. The baseline-corrected AUC0-t will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (corrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estradiol. The baseline-corrected AUC0-t will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total nomegestrol: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total nomegestrol. The AUC0-72 will be calculated.
Measured: From tablet intake and up to 72 hours after tablet intake
Total estrone (corrected): Maximum plasma concentration (Cmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The baseline-corrected Cmax of estrone will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (corrected): Maximum plasma concentration (Cmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The baseline-corrected Cmax of estradiol will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total nomegestrol: Maximum plasma concentration (Cmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The achieved Cmax of nomegestrol will be calculated.
Measured: From tablet intake up to 72 hours after tablet intake
Secondary outcomes (7)
Total estrone: Time to achieve maximum plasma concentration (tmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The tmax of estrone will be calculated.
Measured: From tablet intake up to 72 hours after tablet intake
Total estradiol: Time to achieve maximum plasma concentration (tmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The tmax of estradiol will be calculated.
Measured: From tablet intake up to 72 hours after tablet intake
Total nomegestrol: Time to achieve maximum plasma concentration (tmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The tmax of nomegestrol will be calculated.
Measured: From tablet intake up to 72 hours after tablet intake
Total estrone (uncorrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estrone. The AUC0-t will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (uncorrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estrone. The AUC0-t will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estrone (uncorrected): Maximum plasma concentration (Cmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The achieved Cmax of estrone will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (uncorrected): Maximum plasma concentration (Cmax)
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The achieved Cmax of estradiol will be calculated.
Measured: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study startOct 2019 (estimated)
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BioequivalenceStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grünenthal GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grünenthal, S.A.
- Responsible party
- Sponsor
- Investigators
- Grünenthal Study Director, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03749733
- Sponsor's protocol ID
- ESTNMG-04-GRU
- Other IDs
- HP8010-01, 17-CI-09 012 084
- Status last verified
- Jul 2019
- First submitted
- 9 Nov 2018
- Last updated
- 15 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information available on the Grünenthal Web Site (see URL below for details)
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Site, Open-label, Randomized, Two Treatments, Two Periods, Two Sequences, Crossover Single-dose Trial to Investigate the Bioequivalence of Two Oral Formulations of a Fixed-dose Combination Tablet Containing 1.5 mg Estradiol and 2.5 mg Nomegestrol Acetate (Product of Laboratorios Andrómaco S.A. [Test Product] Versus Stezza, Product of Merck Sharp & Dohme Farmacêutica Ltda. [Reference Product]) in Postmenopausal Women Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT03749733
- Acronym / sponsor ID
- ESTNMG-04-GRU
- Conditions
- Bioequivalence
- Keywords
- Bioequivalence, Estradiol, Nomegestrol acetate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Grünenthal GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Grünenthal, S.A.
- Study start
- Oct 2019 (estimated)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 21 Nov 2018 (actual)
- 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.
This study will investigate the bioavailability in fasting post-menopausal women of 2 film-coated tablet formulations containing 1.5 milligrams (mg) of estradiol and 2.5 mg of nomegestrol acetate.
The study will be performed at a single site. Participants will take a single oral dose of the test product and reference product in 2 periods and 2 sequences (either test after reference or reference after test). There will be a washout of at least 21 days between each study period.
Detailed description
The primary objective of the study is to investigate the relative bioavailability of estradiol and nomegestrol of 2 film-coated tablet formulations with estradiol 1.5 mg and nomegestrol acetate 2.5 mg and to demonstrate bioequivalence of both formulations in terms of rate and extent of absorption:
- Test Product: new product manufactured by Laboratorios Andrómaco S.A.
- Reference Product: Stezza [Trademark], product of Merck Sharp \& Dohme Farmacêutica Ltda.
The 90% confidence intervals for the intra-subject coefficient of variation (Test versus Reference Product) for the main pharmacokinetic parameters area under the plasma concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72 hours (AUC0-72), and maximum plasma concentration (Cmax) for total estradiol/estrone and nomegestrol will be determined.
Participants will be confined in the study site for approximately 36 hours during each study period (for 12 hours pre-dosing and for 24 hours post dosing) during which pharmacokinetic (PK) blood samples will be obtained. Three blood samples will be taken before the film-coated tablet is administered (at pre-dose: -1.0, -0.5, and 0 h) and 16 samples up to 24 hours after the administration in each period. Participants will return to the site to provide additional blood samples at 36 h, 48 h, and 72 h post-dose.
The washout period between the two study periods will be at least 21 days.
The samples from each participant will be analyzed with 2 methods of high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays to quantify total estradiol/estrone and nomegestrol in plasma with citrate phosphate dextrose anticoagulant. The blood samples taken at pre-dose will be taken to establish the baseline concentrations of total estrone and estradiol. The baseline-corrected and uncorrected AUCs and Cmax will be calculated.
The safety objective is to evaluate the tolerability of both formulations in post-menopausal women by collecting adverse events.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test Product | Experimental | Drug: Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product)Participants will receive a single film-coated tablet of the test formulation containing estradiol 1.5 mg/nomegestrol acetate 2.5 mg. The tablet will be taken with water and in a fasting condition. |
| Reference Product | Active comparator | Drug: Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product)Participants will receive a single film-coated tablet of the marketed reference formulation containing estradiol 1.5 mg/nomegestrol acetate 2.5 mg. The tablet will be taken with water and in a fasting condition. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Participation will be voluntary and according to the guidelines proposed by the Health General Law (Mexico), and informed consent will be obtained according to the previously mentioned law. In addition, the study will be conducted according to the ethical principles that have their origin in the Declaration of Helsinki, the current Brazilian laws, and Good Clinical Practice.
- Only post-menopausal women aged between 40 years and 65 years who meet any of the following criteria:
- 12 months of spontaneous amenorrhea.
- 6 months of spontaneous amenorrhea with follicle-stimulating hormone levels above 40 international units per liter and below 20 nanograms per liter estradiol.
- Bilateral oophorectomy with or without hysterectomy.
Key exclusion criteria (30 listed)
- Participants with a history of the following diseases: cardiovascular (myocardial infarction, not-controlled hypertension, thromboembolic arterial or venous diseases), renal (kidney failure), hepatic (hepatitis, jaundice), muscular, metabolic, gastrointestinal, neurologic (cerebrovascular disease), psychiatric (depression) endocrinological (not-controlled diabetes mellitus), hematopoietic, respiratory or other organic abnormalities that are not appropriately controlled and that require a pharmacological treatment that could result in a drug interaction with the study medication. Women who have had muscular trauma within 21 days previous to the study will also be excluded.
- History of major surgeries (cranial surgery, thorax, abdomen or extensive surgeries in extremity requiring the use of general or regional anesthesia and/or respiratory support) within 3 months previous to the study.
- Participants with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer.
- History of lactose intolerance.
- Participants who have been exposed to medications known to be hepatic enzyme inducers or inhibitors within 72 hours previous to the start of the study.
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 |
|---|---|---|
| Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product)Also: Stezza (Trade Mark)Marketed Drug | Drug | Reference Product |
| Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product)Investigational Medicinal Product | Drug | Test Product |
Primary outcome
Total estrone (corrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estrone. The baseline-corrected AUC0-t will be calculated.
Total estradiol (corrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total estradiol. The baseline-corrected AUC0-t will be calculated.
Total nomegestrol: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72)
Time frame: From tablet intake and up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The samples taken at pre-dose will be taken to establish the baseline concentration of total nomegestrol. The AUC0-72 will be calculated.
Total estrone (corrected): Maximum plasma concentration (Cmax)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The baseline-corrected Cmax of estrone will be calculated.
Total estradiol (corrected): Maximum plasma concentration (Cmax)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The baseline-corrected Cmax of estradiol will be calculated.
Total nomegestrol: Maximum plasma concentration (Cmax)
Time frame: From tablet intake up to 72 hours after tablet intake
Three blood samples will be taken before the medication is administered and 19 samples up to 72 hours after the administration in each period. The achieved Cmax of nomegestrol will be calculated.
7 secondary outcomes
Total estrone: Time to achieve maximum plasma concentration (tmax)
Time frame: From tablet intake up to 72 hours after tablet intake
Total estradiol: Time to achieve maximum plasma concentration (tmax)
Time frame: From tablet intake up to 72 hours after tablet intake
Total nomegestrol: Time to achieve maximum plasma concentration (tmax)
Time frame: From tablet intake up to 72 hours after tablet intake
Total estrone (uncorrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (uncorrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estrone (uncorrected): Maximum plasma concentration (Cmax)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Total estradiol (uncorrected): Maximum plasma concentration (Cmax)
Time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2019.
- Individual participant dataSharing planned: Yes. Information available on the Grünenthal Web Site (see URL below for details)
Related trials for Bioequivalence
Not yet recruitingPhase 1
A Study of Imlunestrant (LY3484356) in Healthy Female Participants
Healthy
RecruitingPhase 1
A Randomized, Double-Blind, Positive-Controlled, Parallel Pharmacokinetic Phase I Clinical Study of Cetuximab Injection Versus Erbitux in Healthy Male Subjects
Cetuximab, Bioequivalence
RecruitingPhase 1
Bioequivalence Study Between YHP2508B and YHR2602 in Healthy Subjects
Healthy Subjects (HS)
Active, not recruitingPhase 1
A Study of Comparative Formulations of Niraparib and Abiraterone Acetate (AA) in Men With Prostate Cancer
Prostatic Neoplasms
RecruitingPhase 1
Bioequivalence Study Between YHP2508A and YHR2601 in Healthy Subjects
Healthy Subjects (HS)
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.
Grünenthal Study Director study director
Grünenthal GmbH
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 Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Reference Product) and Estradiol 1.5 mg/nomegestrol acetate 2.5 mg (Test Product) in people with Bioequivalence, run by Grünenthal GmbH at 1 site in Mexico.
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 30 inclusion and 30 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: withdrawn, as of the sponsor's last update on 15 Jul 2019. 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 Mexico. 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 was withdrawn before enrolling participants, so there are no results.
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?
Total estrone (corrected): area under the plasma concentration-time curve from 0 to time t (AUC0-t) (time frame: Blood samples drawn at baseline (up to 1 hour before tablet intake) and up to 72 hours after tablet intake). The study lists 6 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 15 Jul 2019.