Phase 1
N=20
Effect of Evobrutinib on Pharmacokinetics of a Combined Oral Contraceptive
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT07215806 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
Nov 2025
Primary outcome: Primary: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone — 1090; 36000 hour × picogram per milliliter (h×pg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Evobruitnib (Drug); Combined oral contraceptive [ethinyl estradiol/ norethisterone (EE/NET)] (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Ethinyl Estradiol and Norethisterone |
1090; 36000 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethisterone |
51.8; 4620 | — |
| SECONDARY Number of Participants With Treatment- Emergent Adverse Events (TEAEs) |
9 | — |
| SECONDARY Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity |
8; 1; 0 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Hemoglobin at Day 18 |
-8.780 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Erythrocytes at Day 18 |
-0.29 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes at Day 18 |
-18; -0.08; -0.21; -0.00; 0.00; -0.02 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Day 18 |
-0.029; 0.0; 0.0; 3.2; -0.2; -3.0 | — |
| SECONDARY Change From Baseline in Coagulation Parameter: Activated Partial Thromboplastin Time at Day 18 |
-1.6 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin at Day 18 |
-0.06283 | — |
| SECONDARY Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume at Day 18 |
-0.7 | — |
| SECONDARY Change From Baseline in Coagulation Parameter: Prothrombin Intl. Normalized Ratio at Day 18 |
-0.02 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine and Urate at Day 18 |
-0.8; -4; 4.1 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Day 18 |
-2; 3; -4; -1; -2.0; 0 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Sodium, Potassium, Calcium, Glucose, Chloride and Triglycerides at Day 18 |
1; -0.03; -0.04; -0.10; 2; 0.2 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Total Protein at Day 18 |
-2 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: C Reactive Protein at Day 18 |
4 | — |
| SECONDARY Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at Day 18 |
4; 3 | — |
| SECONDARY Change From Baseline in Vital Signs: Pulse Rate at Day 18 |
4 | — |
| SECONDARY Change From Baseline in Vital Signs: Respiratory Rate at Day 18 |
— | — |
| SECONDARY Change From Baseline in Vital Signs: Temperature at Day 18 |
0.2 | — |
| SECONDARY Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate at Day 18 |
-4 | — |
| SECONDARY Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration at Day 18 |
51; 3; -5; 3; -2 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethisterone |
3.00; 2.00 | — |
| SECONDARY Terminal Half Life (T1/2) of Ethinyl Estradiol and Norethisterone |
21.5; 12.7 | — |
| 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 |
964; 35100 | — |
| SECONDARY Apparent Total Body Clearance (CL/f) of Ethinyl Estradiol and Norethisterone |
27.6; 13.9 | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (VZ/f) of Ethinyl Estradiol and Norethisterone |
816; 252 | — |
Summary
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.
* Study Duration: up to 46 days
* Treatment Duration: Days 4 to 17 (14 days treatment with M2951); Days 1 and 15 (2 days treatment with Combined Oral Contraceptive [COC])
* Visit Frequency: Participants were resident in the Clinical Research Unit from Day -1 to Day 18.
Eligibility Criteria
Inclusion Criteria
- Participants are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
- Participants have a body weight within 50.0 and 100.0 kilograms (kg) (inclusive) and body mass index within the range 19.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive)
- Participants are nonsmokers for at least 6 months preceding Screening
- Female participants who are not a Woman of Childbearing Potential (WOCBP)
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
- Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study
- Participants with prior history of splenectomy or any clinically relevant surgery within 3 months prior to Screening
- Participants with history of any malignancy
- Participants with history of chronic or recurrent acute infection or any bacterial, viral, parasitic, or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to Screening
- Participants with history of shingles within 12 months prior to Screening
- Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines [e.g., Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) vaccines] is allowed until 4 weeks before admission to CRU, thereafter it is prohibited until the end of the study
- Note: In case of clinical symptoms, the participant should be symptom-free for at least 1 week prior to admission to Clinical Research Unit (CRU)
- Other protocol defined exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT07215806). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.