Effect of Evobrutinib on Pharmacokinetics of a Combined Oral Contraceptive

NCT07215806 | Completed Phase 1 Results

• 2 other identifiers: MS200527_00792022-000124-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Drug-drug interaction; Clinical pharmacology

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (26)

• Number of Participants With Treatment- Emergent Adverse Events (TEAEs)

  Up to 46 days

• Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity

  Up to 46 days

• Change From Baseline in Hematology Parameter: Hemoglobin at Day 18

  Baseline, Day 18

• Change From Baseline in Hematology Parameter: Erythrocytes at Day 18

  Baseline, Day 18

• Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Lymphocytes at Day 18

  Baseline, Day 18

Study Arms (1)

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.

Drug: Evobruitnib; Drug: Combined oral contraceptive [ethinyl estradiol/ norethisterone (EE/NET)]

Interventions

Evobruitnib DRUG

Participants received Evobruitnib at a dose of 45 mg orally twice daily on Days 4 to 17.

COC + Evobrutinib

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.

COC + Evobrutinib

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, Germany

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Interventions

Contraceptives, Oral, Combined; Ethinyl Estradiol; Norethindrone

Intervention Hierarchy (Ancestors)

Drug Combinations; Pharmaceutical Preparations; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norpregnenes

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2025
• First Posted: October 14, 2025
• Study Start: August 24, 2022
• Primary Completion: November 25, 2022
• Study Completion: November 25, 2022
• Last Updated: November 14, 2025
• Results First Posted: November 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)