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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-000124-38 | EudraCT Number |
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The purpose of this study was to assess the effect of M2951 on the pharmacokinetics (PK) of a combined oral contraceptive [Ethinyl estradiol/Norethisterone (EE/NET)] in healthy female participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| COC + Evobrutinib | Experimental | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evobruitnib | Drug | Participants received Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethisterone | Cmax was obtained directly from the concentration versus time curve. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment- Emergent Adverse Events (TEAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nuvisan GmbH | Neu-Ulm | Germany |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| Medical Information Location Map - Med Info Contacts | View source |
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We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21
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| ID | Title | Description |
|---|---|---|
| FG000 | COC + Evobrutinib | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | COC + Evobrutinib | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. | Pharmacokinetics (PK) Analysis set included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Geometric Mean | Geometric Coefficient of Variation | hour × picogram per milliliter (h×pg/mL) | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
Up to 46 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | COC + Evobrutinib | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal faeces | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 20, 2022 | Oct 29, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 13, 2022 | Oct 29, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003277 | Contraceptives, Oral, Combined |
| D004997 | Ethinyl Estradiol |
| D009640 | Norethindrone |
| ID | Term |
|---|---|
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D003276 | Contraceptives, Oral |
| D003271 | Contraceptive Agents, Female |
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| Combined oral contraceptive [ethinyl estradiol/ norethisterone (EE/NET)] | Drug | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15. |
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| Up to 46 days |
| Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity | The Investigator assessed the severity of each AE and SAE reported during the study and assign it to one of the following categories: Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities; Severe: An event that prevents normal everyday activities. Do not confuse an AE that is assessed as severe with a SAE. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe. | Up to 46 days |
| Change From Baseline in Hematology Parameter: Hemoglobin at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: hemoglobin. | Baseline, Day 18 |
| Change From Baseline in Hematology Parameter: Erythrocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes. | Baseline, Day 18 |
| Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes. | Baseline, Day 18 |
| Change From Baseline in Hematology Parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes. | Baseline, Day 18 |
| Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the coagulation parameter: Activated Partial Thromboplastin Time. | Baseline, Day 18 |
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. | Baseline, Day 18 |
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. | Baseline, Day 18 |
| Change From Baseline in Coagulation Parameter: Prothrombin Intl. Normalized Ratio at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the coagulation parameter: Prothrombin Intl. Normalized Ratio. | Baseline, Day 18 |
| Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: bilirubin, creatinine and urate. | Baseline, Day 18 |
| Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase. | Baseline, Day 18 |
| Change From Baseline in Chemistry Parameters: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides. | Baseline, Day 18 |
| Change From Baseline in Chemistry Parameters: Total Protein at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Total Protein. | Baseline, Day 18 |
| Change From Baseline in Chemistry Parameters: C Reactive Protein at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: C Reactive Protein. | Baseline, Day 18 |
| Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at Day 18 | Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Baseline, Day 18 |
| Change From Baseline in Vital Signs: Pulse Rate at Day 18 | Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Baseline, Day 18 |
| Change From Baseline in Vital Signs: Respiratory Rate at Day 18 | Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Baseline, Day 18 |
| Change From Baseline in Vital Signs: Temperature at Day 18 | Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Baseline, Day 18 |
| Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate at Day 18 | Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions | Baseline, Day 18 |
| Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration at Day 18 | RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Baseline, Day 18 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethisterone | Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Terminal Half Life (T1/2) of Ethinyl Estradiol and Norethisterone | Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Ethinyl Estradiol and Norethisterone | The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Apparent Total Body Clearance (CL/f) of Ethinyl Estradiol and Norethisterone | Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Ethinyl Estradiol/Norethisterone. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Apparent Volume of Distribution During Terminal Phase (VZ/f) of Ethinyl Estradiol and Norethisterone | Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Ethinyl Estradiol/Norethisterone. | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| ID | Title | Description |
|---|
| OG000 | COC + Evobrutinib | Participants received combined oral contraceptive (COC) [0.03 milligrams (mg) of Ethinyl Estradiol (EE)], 0.5 mg of Norethisterone (NET)] orally on Day 1 and 15 in combination with Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17. |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethisterone | Cmax was obtained directly from the concentration versus time curve. | Pharmacokinetics (PK) Analysis set included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
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| Secondary | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Up to 46 days |
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| Secondary | Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity | The Investigator assessed the severity of each AE and SAE reported during the study and assign it to one of the following categories: Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities; Severe: An event that prevents normal everyday activities. Do not confuse an AE that is assessed as severe with a SAE. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Up to 46 days |
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| Secondary | Change From Baseline in Hematology Parameter: Hemoglobin at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: hemoglobin. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | gram per liter (g/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Baseline, Day 18 |
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| Secondary | Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline, Day 18 |
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| Secondary | Change From Baseline in Hematology Parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | percentage of cells | Baseline, Day 18 |
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| Secondary | Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the coagulation parameter: Activated Partial Thromboplastin Time. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | seconds | Baseline, Day 18 |
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| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | picogram | Baseline, Day 18 |
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| Secondary | Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | femtoliters | Baseline, Day 18 |
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| Secondary | Change From Baseline in Coagulation Parameter: Prothrombin Intl. Normalized Ratio at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the coagulation parameter: Prothrombin Intl. Normalized Ratio. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | ratio | Baseline, Day 18 |
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| Secondary | Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: bilirubin, creatinine and urate. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | micromole per liter (mcmol/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | units per liter (U/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Chemistry Parameters: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | millimoles per liter (mmol/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Chemistry Parameters: Total Protein at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: Total Protein. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | gram per liter (g/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Chemistry Parameters: C Reactive Protein at Day 18 | Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the chemistry parameter: C Reactive Protein. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | milligram per liter (g/L) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at Day 18 | Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | Baseline, Day 18 |
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| Secondary | Change From Baseline in Vital Signs: Pulse Rate at Day 18 | Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Day 18 |
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| Secondary | Change From Baseline in Vital Signs: Respiratory Rate at Day 18 | Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | breaths per minute | Baseline, Day 18 |
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| Secondary | Change From Baseline in Vital Signs: Temperature at Day 18 | Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | degree Celsius | Baseline, Day 18 |
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| Secondary | Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate at Day 18 | Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Day 18 |
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| Secondary | Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration at Day 18 | RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. | Safety (SAF) analysis set included all participants, who were administered any dose of any study intervention. | Posted | Mean | Standard Deviation | milliseconds (msec) | Baseline, Day 18 |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethisterone | Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | Pharmacokinetics (PK) Analysis set included all participants: who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Median | Full Range | hours | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
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| Secondary | Terminal Half Life (T1/2) of Ethinyl Estradiol and Norethisterone | Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve. | Pharmacokinetics (PK) Analysis set included all participants: who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Median | Full Range | hours | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
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| Secondary | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Ethinyl Estradiol and Norethisterone | The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down). | Pharmacokinetics (PK) Analysis set included all participants: who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Geometric Mean | Geometric Coefficient of Variation | h×pg/mL | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
|
|
|
| Secondary | Apparent Total Body Clearance (CL/f) of Ethinyl Estradiol and Norethisterone | Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Ethinyl Estradiol/Norethisterone. | Pharmacokinetics (PK) Analysis set included all participants: who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
|
|
|
| Secondary | Apparent Volume of Distribution During Terminal Phase (VZ/f) of Ethinyl Estradiol and Norethisterone | Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Ethinyl Estradiol/Norethisterone. | Pharmacokinetics (PK) Analysis set included all participants: who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results; with adequate study intervention compliance; with evaluable PK data, i.e., no missing values for primary endpoints at each PK profile/assessment day (Day 1, Day 15). | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Pre-dose, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours post-dose on Days 1, 2, 3, 4, 15, 16, 17 and 18 |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 9 |
| 20 |
| Defaecation urgency | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 25.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Restless legs syndrome | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Polymenorrhoea | Reproductive system and breast disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
Not provided
Not provided
| D003270 | Contraceptive Agents |
| D012102 | Reproductive Control Agents |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045506 | Therapeutic Uses |
| D009651 | Norpregnatrienes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D042782 | Estrogenic Steroids, Alkylated |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009652 | Norpregnenes |
| Title | Measurements |
|---|
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| Title | Measurements |
|---|---|
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| Eosinophils |
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| Basophils |
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| Monocytes |
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| Lymphocytes |
|
| Title | Measurements |
|---|---|
|
| Lymphocytes/Leukocytes |
|
| Monocytes/Leukocytes |
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| Neutrophils/Leukocytes |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
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| Amylase |
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| Lipase |
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| Gamma Glutamyl Transferase |
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| Lactate Dehydrogenase |
|
| Title | Measurements |
|---|---|
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| Glucose |
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| Chloride |
|
| Triglycerides |
|
| Title | Measurements |
|---|---|
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| PR Duration |
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| QRS Duration |
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